Variant 6-159169681-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000297267.14(FNDC1):c.85G>T(p.Val29Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,161,340 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00082 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

FNDC1
ENST00000297267.14 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.738

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027558476).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FNDC1	NM_032532.3 linkuse as main transcript	c.85G>T	p.Val29Phe	missense_variant	1/23	ENST00000297267.14	NP_115921.2
FNDC1-AS1	NR_121668.1 linkuse as main transcript	n.196+131C>A		intron_variant, non_coding_transcript_variant
FNDC1	XM_011536190.3 linkuse as main transcript	c.85G>T	p.Val29Phe	missense_variant	1/22		XP_011534492.1
FNDC1	XM_011536191.3 linkuse as main transcript	c.85G>T	p.Val29Phe	missense_variant	1/20		XP_011534493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC1	ENST00000297267.14 linkuse as main transcript	c.85G>T	p.Val29Phe	missense_variant	1/23	1	NM_032532.3	ENSP00000297267	P1	Q4ZHG4-1
FNDC1-AS1	ENST00000608986.1 linkuse as main transcript	n.196+131C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000821

AC:

124

AN:

151048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00284

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000329

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00645

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000426

AC:

AN:

1010186

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

476556

show subpopulations

Gnomad4 AFR exome

AF:

0.00177

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:

0.00

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.000820

AC:

124

AN:

151154

Hom.:

Cov.:

AF XY:

0.000717

AC XY:

AN XY:

73890

show subpopulations

Gnomad4 AFR

AF:

0.00283

Gnomad4 AMR

AF:

0.000329

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000713

Hom.:

Bravo

AF:

0.000756

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

Oct 20, 2021

The c.85G>T (p.V29F) alteration is located in exon 1 (coding exon 1) of the FNDC1 gene. This alteration results from a G to T substitution at nucleotide position 85, causing the valine (V) at amino acid position 29 to be replaced by a phenylalanine (F). 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

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.44

M_CAP

Benign

0.031

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.27

REVEL

Benign

0.036

Sift

Uncertain

0.013

Sift4G

Uncertain

0.035

Polyphen

0.075

Vest4

0.23

MutPred

0.38

Gain of helix (P = 0.062);

MVP

0.34

MPC

0.22

ClinPred

0.19

GERP RS

1.5

Varity_R

0.18

gMVP

0.38

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