Variant 20-56526047-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001012971.4(FAM209A):c.493T>C(p.Trp165Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,606,952 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 1 hom. )

Consequence

FAM209A
NM_001012971.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

FAM209A (HGNC:16100): (family with sequence similarity 209 member A) Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM209A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15734011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM209A	NM_001012971.4 link	c.493T>C	p.Trp165Arg	missense_variant	2/2	ENST00000371328.5	NP_001012989.2	Q5JX71
FAM209A	XM_047439964.1 link	c.493T>C	p.Trp165Arg	missense_variant	2/5		XP_047295920.1
FAM209A	XM_047439965.1 link	c.493T>C	p.Trp165Arg	missense_variant	2/6		XP_047295921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM209A	ENST00000371328.5 link	c.493T>C	p.Trp165Arg	missense_variant	2/2	1	NM_001012971.4	ENSP00000360379.4		Q5JX71
FAM209A	ENST00000481560.1 link	n.638T>C		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000134

AC:

AN:

246832

Hom.:

AF XY:

0.000105

AC XY:

AN XY:

133270

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.000209

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000619

AC:

AN:

1454722

Hom.:

Cov.:

AF XY:

0.0000650

AC XY:

AN XY:

722746

show subpopulations

Gnomad4 AFR exome

AF:

0.00160

Gnomad4 AMR exome

AF:

0.000182

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000824

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.000300

GnomAD4 genome

AF:

0.000565

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.000196

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:

0.000473

Alfa

AF:

0.0000394

Hom.:

Bravo

AF:

0.000672

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000123

AC:

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

Jun 09, 2022

The c.493T>C (p.W165R) alteration is located in exon 2 (coding exon 2) of the FAM209A gene. This alteration results from a T to C substitution at nucleotide position 493, causing the tryptophan (W) at amino acid position 165 to be replaced by an arginine (R). 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

0.26

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.41

DEOGEN2

Benign

0.070

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.43

M_CAP

Benign

0.0023

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PROVEAN

Pathogenic

-9.5

REVEL

Benign

0.20

Sift

Benign

0.030

Sift4G

Uncertain

0.056

Polyphen

0.89

Vest4

0.59

MutPred

0.46

Gain of disorder (P = 0);

MVP

0.11

MPC

0.38

ClinPred

0.12

GERP RS

2.8

Varity_R

0.15

gMVP

0.27

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