Variant chr6-159169697-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032532.3(FNDC1):c.101C>A(p.Ala34Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000995 in 1,004,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

FNDC1
NM_032532.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.212

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:

FNDC1-AS1 (HGNC:55706): (FNDC1 antisense RNA 1)

FNDC1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05272436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FNDC1	NM_032532.3 linkuse as main transcript	c.101C>A	p.Ala34Glu	missense_variant	1/23	ENST00000297267.14
FNDC1-AS1	NR_121668.1 linkuse as main transcript	n.196+115G>T		intron_variant, non_coding_transcript_variant
FNDC1	XM_011536190.3 linkuse as main transcript	c.101C>A	p.Ala34Glu	missense_variant	1/22
FNDC1	XM_011536191.3 linkuse as main transcript	c.101C>A	p.Ala34Glu	missense_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC1	ENST00000297267.14 linkuse as main transcript	c.101C>A	p.Ala34Glu	missense_variant	1/23	1	NM_032532.3	P1	Q4ZHG4-1
FNDC1-AS1	ENST00000608986.1 linkuse as main transcript	n.196+115G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.95e-7

AC:

AN:

1004926

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

474286

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:

0.00000115

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 28, 2021

The c.101C>A (p.A34E) alteration is located in exon 1 (coding exon 1) of the FNDC1 gene. This alteration results from a C to A substitution at nucleotide position 101, causing the alanine (A) at amino acid position 34 to be replaced by a glutamic acid (E). 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

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0087

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.21

M_CAP

Benign

0.0057

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.060

REVEL

Benign

0.0080

Sift

Benign

0.29

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.20

MutPred

0.34

Gain of sheet (P = 0.0125);

MVP

0.35

MPC

0.19

ClinPred

0.19

GERP RS

1.8

Varity_R

0.059

gMVP

0.32

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