Genetic Variant NM_004629.2:c.1157C>T (chr9-35075741-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004629.2(FANCG):c.1157C>T(p.Pro386Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 460,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P386R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

FANCG
NM_004629.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.207

Publications

4 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: G2P, ClinGen, 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.081136554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCG	NM_004629.2 link	c.1157C>T	p.Pro386Leu	missense_variant	Exon 10 of 14	ENST00000378643.8	NP_004620.1	O15287Q53XM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCG	ENST00000378643.8 link	c.1157C>T	p.Pro386Leu	missense_variant	Exon 10 of 14	1	NM_004629.2	ENSP00000367910.4		O15287

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

232370

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

460824

Hom.:

Cov.:

AF XY:

0.0000199

AC XY:

AN XY:

251034

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12430

American (AMR)

AF:

0.00

AC:

AN:

35902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13584

East Asian (EAS)

AF:

0.0000565

AC:

AN:

17702

South Asian (SAS)

AF:

0.0000148

AC:

AN:

67342

European-Finnish (FIN)

AF:

0.0000318

AC:

AN:

31488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3114

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

258510

Other (OTH)

AF:

0.00

AC:

AN:

20752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.0

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.27

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.69

M_CAP

Benign

0.021

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

0.21

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.2

REVEL

Benign

0.032

Sift

Benign

0.10

Sift4G

Benign

0.12

Polyphen

0.041

Vest4

0.15

MutPred

0.28

Loss of glycosylation at P386 (P = 0.0046);

MVP

0.41

MPC

0.22

ClinPred

0.070

GERP RS

1.4

Varity_R

0.024

gMVP

0.19

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over