Genetic Variant FNDC3A:p.Ser275Ser (chr13-49145783-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001079673.2(FNDC3A):c.825C>T(p.Ser275Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00508 in 1,613,194 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0095 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 36 hom. )

Consequence

FNDC3A
NM_001079673.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.851

Variant links:

Genes affected

FNDC3A (HGNC:20296): (fibronectin type III domain containing 3A) Enables RNA binding activity. Predicted to act upstream of or within several processes, including Sertoli cell development; fertilization; and spermatid development. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

FNDC3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 13-49145783-C-T is Benign according to our data. Variant chr13-49145783-C-T is described in ClinVar as [Benign]. Clinvar id is 768616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.851 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00955 (1453/152160) while in subpopulation AFR AF= 0.0227 (944/41498). AF 95% confidence interval is 0.0215. There are 14 homozygotes in gnomad4. There are 688 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNDC3A	NM_001079673.2 link	c.825C>T	p.Ser275Ser	synonymous_variant	Exon 8 of 26	ENST00000492622.6	NP_001073141.1	Q9Y2H6-1A0A024RDT9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNDC3A	ENST00000492622.6 link	c.825C>T	p.Ser275Ser	synonymous_variant	Exon 8 of 26	1	NM_001079673.2	ENSP00000417257.1		Q9Y2H6-1

Frequencies

GnomAD3 genomes

AF:

0.00954

AC:

1451

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00746

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00541

AC:

1357

AN:

250716

Hom.:

AF XY:

0.00481

AC XY:

652

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.0216

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.00675

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000460

Gnomad FIN exome

AF:

0.00878

Gnomad NFE exome

AF:

0.00497

Gnomad OTH exome

AF:

0.00540

GnomAD4 exome

AF:

0.00462

AC:

6749

AN:

1461034

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

3242

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.0233

Gnomad4 AMR exome

AF:

0.00370

Gnomad4 ASJ exome

AF:

0.00662

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000604

Gnomad4 FIN exome

AF:

0.00910

Gnomad4 NFE exome

AF:

0.00426

Gnomad4 OTH exome

AF:

0.00500

GnomAD4 genome

AF:

0.00955

AC:

1453

AN:

152160

Hom.:

Cov.:

AF XY:

0.00925

AC XY:

688

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0227

Gnomad4 AMR

AF:

0.00530

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00746

Gnomad4 NFE

AF:

0.00453

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00721

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00600

EpiControl

AF:

0.00451

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.9

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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