Genetic Variant FNDC8:p.Met41Val (chr17-35121814-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_017559.4(FNDC8):c.121A>G(p.Met41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,613,648 control chromosomes in the GnomAD database, including 3 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

FNDC8
NM_017559.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

FNDC8 (HGNC:25286): (fibronectin type III domain containing 8) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FNDC8 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=0.006964892).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNDC8	NM_017559.4 link	c.121A>G	p.Met41Val	missense_variant	Exon 1 of 4	ENST00000158009.6	NP_060029.1	Q8TC99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNDC8	ENST00000158009.6 link	c.121A>G	p.Met41Val	missense_variant	Exon 1 of 4	1	NM_017559.4	ENSP00000158009.4		Q8TC99

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

198

AN:

151824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00624

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.00123

AC:

310

AN:

251446

Hom.:

AF XY:

0.00130

AC XY:

177

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00499

Gnomad NFE exome

AF:

0.00149

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00154

AC:

2248

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

1069

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00425

Gnomad4 NFE exome

AF:

0.00171

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00130

AC:

198

AN:

151824

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74132

show subpopulations

Gnomad4 AFR

AF:

0.000387

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00624

Gnomad4 NFE

AF:

0.00160

Gnomad4 OTH

AF:

0.000481

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000880

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00102

AC:

124

EpiCase

AF:

0.00153

EpiControl

AF:

0.00237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 4

Uncertain:1

May 28, 2019

Mendelics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.026

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.054

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.45

M_CAP

Benign

0.0052

MetaRNN

Benign

0.0070

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.88

REVEL

Benign

0.046

Sift

Uncertain

0.019

Sift4G

Benign

0.087

Polyphen

0.033

Vest4

0.12

MVP

0.34

MPC

0.13

ClinPred

0.015

GERP RS

3.6

Varity_R

0.24

gMVP

0.18

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