Variant 6-159197515-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032532.3(FNDC1):c.194C>A(p.Ala65Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

FNDC1
NM_032532.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85

Variant links:

Genes affected

FNDC1 (HGNC:21184): (fibronectin type III domain containing 1) Predicted to act upstream of or within several processes, including cellular response to hypoxia; positive regulation of cardiac muscle cell apoptotic process; and positive regulation of protein phosphorylation. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

FNDC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FNDC1	NM_032532.3 linkuse as main transcript	c.194C>A	p.Ala65Asp	missense_variant	2/23	ENST00000297267.14
FNDC1	XM_011536190.3 linkuse as main transcript	c.194C>A	p.Ala65Asp	missense_variant	2/22
FNDC1	XM_011536191.3 linkuse as main transcript	c.110-17430C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC1	ENST00000297267.14 linkuse as main transcript	c.194C>A	p.Ala65Asp	missense_variant	2/23	1	NM_032532.3	P1	Q4ZHG4-1
FNDC1	ENST00000329629.8 linkuse as main transcript	c.71C>A	p.Ala24Asp	missense_variant	1/21	1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 21, 2023

The c.194C>A (p.A65D) alteration is located in exon 2 (coding exon 2) of the FNDC1 gene. This alteration results from a C to A substitution at nucleotide position 194, causing the alanine (A) at amino acid position 65 to be replaced by an aspartic acid (D). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0087

Eigen

Benign

0.020

Eigen_PC

Benign

0.089

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.69

M_CAP

Benign

0.0045

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

0.95

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.3

REVEL

Benign

0.19

Sift

Uncertain

0.026

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.60

MutPred

0.33

Gain of disorder (P = 0.0757);

MVP

0.73

MPC

0.24

ClinPred

0.88

GERP RS

6.1

Varity_R

0.26

gMVP

0.55

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