Genetic Variant FNDC11:p.Ala264Val (chr20-63556454-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001319152.2(FNDC11):c.791C>T(p.Ala264Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,613,546 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 4 hom. )

Consequence

FNDC11
NM_001319152.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.824

Variant links:

Genes affected

FNDC11 (HGNC:28764): (fibronectin type III domain containing 11)

FNDC11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007717967).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNDC11	NM_001319152.2 link	c.791C>T	p.Ala264Val	missense_variant	Exon 2 of 2	ENST00000370097.2	NP_001306081.1	Q9BVV2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FNDC11	ENST00000370097.2 link	c.791C>T	p.Ala264Val	missense_variant	Exon 2 of 2	2	NM_001319152.2	ENSP00000359115.1	Q9BVV2
FNDC11	ENST00000370098.4 link	c.791C>T	p.Ala264Val	missense_variant	Exon 2 of 2	1		ENSP00000359116.3	Q9BVV2
FNDC11	ENST00000615526.1 link	c.791C>T	p.Ala264Val	missense_variant	Exon 1 of 1	6		ENSP00000480914.1	Q9BVV2

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

158

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00157

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00110

AC:

276

AN:

251096

Hom.:

AF XY:

0.00103

AC XY:

140

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00151

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00137

AC:

2003

AN:

1461216

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

965

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00264

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000398

Gnomad4 NFE exome

AF:

0.00161

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00104

AC:

158

AN:

152330

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00157

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.00119

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000988

AC:

120

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.791C>T (p.A264V) alteration is located in exon 2 (coding exon 1) of the FNDC11 gene. This alteration results from a C to T substitution at nucleotide position 791, causing the alanine (A) at amino acid position 264 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.088

T;T;T

Eigen

Benign

0.054

Eigen_PC

Benign

0.082

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.66

.;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.0077

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.43

N;.;N

REVEL

Benign

0.12

Sift

Benign

0.12

T;.;T

Sift4G

Uncertain

0.043

D;D;D

Polyphen

0.89

P;P;P

Vest4

0.29

MVP

0.21

MPC

0.63

ClinPred

0.021

GERP RS

5.3

Varity_R

0.050

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over