Genetic Variant FAM47A:p.Arg576Gly (chrX-34130553-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_203408.4(FAM47A):c.1726C>G(p.Arg576Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,209,657 control chromosomes in the GnomAD database, including 31 homozygotes. There are 579 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0098 ( 9 hom., 270 hem., cov: 22)

Exomes 𝑓: 0.0012 ( 22 hom. 309 hem. )

Consequence

FAM47A
NM_203408.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.646

Variant links:

Genes affected

FAM47A (HGNC:29962): (family with sequence similarity 47 member A)

FAM47A links:

ENSG00000233928 (HGNC:):

ENSG00000233928 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003322959).

BP6

Variant X-34130553-G-C is Benign according to our data. Variant chrX-34130553-G-C is described in ClinVar as [Benign]. Clinvar id is 3038371.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00985 (1097/111421) while in subpopulation AFR AF= 0.034 (1044/30671). AF 95% confidence interval is 0.0323. There are 9 homozygotes in gnomad4. There are 270 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47A	NM_203408.4 link	c.1726C>G	p.Arg576Gly	missense_variant	Exon 1 of 1	ENST00000346193.5	NP_981953.2	Q5JRC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47A	ENST00000346193.5 link	c.1726C>G	p.Arg576Gly	missense_variant	Exon 1 of 1	6	NM_203408.4	ENSP00000345029.3		Q5JRC9

Frequencies

GnomAD3 genomes

AF:

0.00978

AC:

1089

AN:

111366

Hom.:

Cov.:

AF XY:

0.00784

AC XY:

263

AN XY:

33558

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00401

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000384

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00469

GnomAD3 exomes

AF:

0.00265

AC:

482

AN:

182189

Hom.:

AF XY:

0.00172

AC XY:

116

AN XY:

67613

show subpopulations

Gnomad AFR exome

AF:

0.0351

Gnomad AMR exome

AF:

0.00117

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:

0.0000858

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.00117

AC:

1280

AN:

1098236

Hom.:

Cov.:

AF XY:

0.000850

AC XY:

309

AN XY:

363592

show subpopulations

Gnomad4 AFR exome

AF:

0.0395

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000416

Gnomad4 OTH exome

AF:

0.00297

GnomAD4 genome

AF:

0.00985

AC:

1097

AN:

111421

Hom.:

Cov.:

AF XY:

0.00803

AC XY:

270

AN XY:

33623

show subpopulations

Gnomad4 AFR

AF:

0.0340

Gnomad4 AMR

AF:

0.00400

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000386

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00462

Alfa

AF:

0.00146

Hom.:

Bravo

AF:

0.0113

ESP6500AA

AF:

0.0283

AC:

106

ESP6500EA

AF:

0.000150

AC:

ExAC

AF:

0.00319

AC:

387

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FAM47A-related disorder

Benign:1

May 31, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.96

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.51

DANN

Benign

0.35

DEOGEN2

Benign

0.0015

T;.

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.29

T;T

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.31

PROVEAN

Benign

0.050

N;.

REVEL

Benign

0.0090

Sift

Benign

0.56

T;.

Sift4G

Benign

0.42

T;T

Polyphen

0.0040

B;.

Vest4

0.053

MVP

0.043

MPC

0.25

ClinPred

0.0023

GERP RS

-1.0

Varity_R

0.056

gMVP

0.078

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