NM_021922.3:c.611C>T

Variant names:

Variant summary

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

The NM_021922.3(FANCE):c.611C>T(p.Ser204Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,613,970 control chromosomes in the GnomAD database, including 513 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 180 hom., cov: 31)

Exomes 𝑓: 0.016 ( 333 hom. )

Consequence

FANCE
NM_021922.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:10O:1

Conservation

PhyloP100: 0.589

Publications

21 publications found

Variant links:

Genes affected

FANCE (HGNC:3586): (FA complementation group E) 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 E. [provided by RefSeq, Jul 2008]

FANCE Gene-Disease associations (from GenCC):

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

FANCE 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=0.0015524924).

BP6

Variant 6-35456109-C-T is Benign according to our data. Variant chr6-35456109-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 134333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021922.3. 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
	FANCE	NM_021922.3	MANE Select	c.611C>T	p.Ser204Leu	missense	Exon 2 of 10	NP_068741.1	Q9HB96
	FANCE	NM_001410876.1		c.611C>T	p.Ser204Leu	missense	Exon 2 of 8	NP_001397805.1	A0A8Q3WL50

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FANCE	ENST00000229769.3	TSL:1 MANE Select	c.611C>T	p.Ser204Leu	missense	Exon 2 of 10	ENSP00000229769.2	Q9HB96
FANCE	ENST00000854656.1		c.611C>T	p.Ser204Leu	missense	Exon 2 of 10	ENSP00000524715.1
FANCE	ENST00000854658.1		c.611C>T	p.Ser204Leu	missense	Exon 2 of 10	ENSP00000524717.1

Frequencies

GnomAD3 genomes

AF:

0.0352

AC:

5359

AN:

152048

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0956

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0161

Gnomad OTH

AF:

0.0254

GnomAD2 exomes

AF:

0.0156

AC:

3920

AN:

251198

AF XY:

0.0133

show subpopulations

Gnomad AFR exome

AF:

0.0973

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.0159

Gnomad OTH exome

AF:

0.00898

GnomAD4 exome

AF:

0.0155

AC:

22659

AN:

1461804

Hom.:

333

Cov.:

AF XY:

0.0147

AC XY:

10721

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.0999

AC:

3343

AN:

33478

American (AMR)

AF:

0.0114

AC:

510

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000974

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00238

AC:

127

AN:

53374

Middle Eastern (MID)

AF:

0.0180

AC:

104

AN:

5768

European-Non Finnish (NFE)

AF:

0.0157

AC:

17475

AN:

1111986

Other (OTH)

AF:

0.0157

AC:

948

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1371

2742

4112

5483

6854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.0352

AC:

5358

AN:

152166

Hom.:

180

Cov.:

AF XY:

0.0330

AC XY:

2455

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0954

AC:

3957

AN:

41496

American (AMR)

AF:

0.0137

AC:

209

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00124

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0161

AC:

1096

AN:

68006

Other (OTH)

AF:

0.0251

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

257

513

770

1026

1283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0219

Hom.:

188

Bravo

AF:

0.0393

TwinsUK

AF:

0.0191

AC:

ALSPAC

AF:

0.0166

AC:

ESP6500AA

AF:

0.0971

AC:

428

ESP6500EA

AF:

0.0142

AC:

122

ExAC

AF:

0.0175

AC:

2126

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0124

EpiControl

AF:

0.0166

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Fanconi anemia complementation group E (4)

not specified (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.066

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.59

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.0

REVEL

Benign

0.15

Sift

Benign

0.22

Sift4G

Uncertain

0.012

Polyphen

0.0

Vest4

0.043

MPC

0.093

ClinPred

0.0031

GERP RS

3.7

Varity_R

0.041

gMVP

0.12

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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