NM_004629.2:c.890C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004629.2(FANCG):c.890C>T(p.Thr297Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,614,128 control chromosomes in the GnomAD database, including 609 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T297A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.029 ( 170 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 439 hom. )

Consequence

FANCG
NM_004629.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:16O:1

Conservation

PhyloP100: 1.27

Publications

24 publications found

Variant links:

Genes affected

FANCG (HGNC:3588): (FA complementation group G) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group G. [provided by RefSeq, Jul 2008]

FANCG Gene-Disease associations (from GenCC):

Fanconi anemia complementation group G
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FANCG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016728342).

BP6

Variant 9-35076758-G-A is Benign according to our data. Variant chr9-35076758-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 134367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004629.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCG	NM_004629.2	MANE Select	c.890C>T	p.Thr297Ile	missense	Exon 7 of 14	NP_004620.1	O15287

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FANCG	ENST00000378643.8	TSL:1 MANE Select	c.890C>T	p.Thr297Ile	missense	Exon 7 of 14	ENSP00000367910.4	O15287
FANCG	ENST00000425676.5	TSL:1	n.*366C>T		non_coding_transcript_exon	Exon 6 of 13	ENSP00000412793.1	F8WC08
FANCG	ENST00000425676.5	TSL:1	n.*366C>T		3_prime_UTR	Exon 6 of 13	ENSP00000412793.1	F8WC08

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

4480

AN:

152116

Hom.:

171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0878

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0507

Gnomad SAS

AF:

0.0497

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0154

AC:

3867

AN:

251494

AF XY:

0.0152

show subpopulations

Gnomad AFR exome

AF:

0.0907

Gnomad AMR exome

AF:

0.00503

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.0298

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00134

Gnomad OTH exome

AF:

0.00945

GnomAD4 exome

AF:

0.00859

AC:

12564

AN:

1461894

Hom.:

439

Cov.:

AF XY:

0.00927

AC XY:

6740

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0961

AC:

3216

AN:

33480

American (AMR)

AF:

0.00539

AC:

241

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26136

East Asian (EAS)

AF:

0.0761

AC:

3020

AN:

39700

South Asian (SAS)

AF:

0.0434

AC:

3740

AN:

86258

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00954

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00132

AC:

1471

AN:

1112012

Other (OTH)

AF:

0.0132

AC:

798

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

874

1749

2623

3498

4372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0294

AC:

4481

AN:

152234

Hom.:

170

Cov.:

AF XY:

0.0302

AC XY:

2249

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0876

AC:

3636

AN:

41512

American (AMR)

AF:

0.0120

AC:

184

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.0508

AC:

263

AN:

5174

South Asian (SAS)

AF:

0.0495

AC:

239

AN:

4826

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00153

AC:

104

AN:

68028

Other (OTH)

AF:

0.0223

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

200

400

599

799

999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0121

Hom.:

198

Bravo

AF:

0.0321

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.0815

AC:

359

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.0177

AC:

2150

Asia WGS

AF:

0.0590

AC:

203

AN:

3478

EpiCase

AF:

0.00213

EpiControl

AF:

0.00160

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fanconi anemia complementation group G (5)

Fanconi anemia (3)

not provided (3)

not specified (4)

Amyotrophic Lateral Sclerosis, Dominant (1)

FANCG-related disorder (1)

Inclusion Body Myopathy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.14

Eigen_PC

Benign

0.032

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

1.3

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

REVEL

Benign

0.043

Sift

Benign

0.057

Sift4G

Uncertain

0.041

Polyphen

0.28

Vest4

0.056

MPC

0.35

ClinPred

0.0082

GERP RS

4.5

Varity_R

0.035

gMVP

0.095

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over