Genetic Variant FAM47A:p.Asp731Gly (chrX-34130087-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_203408.4(FAM47A):c.2192A>G(p.Asp731Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,209,416 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., 19 hem., cov: 23)

Exomes 𝑓: 0.000057 ( 0 hom. 18 hem. )

Consequence

FAM47A
NM_203408.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01307115).

BS2

High Hemizygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47A	NM_203408.4 link	c.2192A>G	p.Asp731Gly	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.2192A>G	p.Asp731Gly	missense_variant	Exon 1 of 1	6	NM_203408.4	ENSP00000345029.3		Q5JRC9

Frequencies

GnomAD3 genomes

AF:

0.000615

AC:

AN:

112136

Hom.:

Cov.:

AF XY:

0.000554

AC XY:

AN XY:

34292

show subpopulations

Gnomad AFR

AF:

0.00214

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000283

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:

0.00

GnomAD3 exomes

AF:

0.000171

AC:

AN:

181399

Hom.:

AF XY:

0.000152

AC XY:

AN XY:

65989

show subpopulations

Gnomad AFR exome

AF:

0.00206

Gnomad AMR exome

AF:

0.000148

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:

0.00

GnomAD4 exome

AF:

0.0000574

AC:

AN:

1097225

Hom.:

Cov.:

AF XY:

0.0000496

AC XY:

AN XY:

362623

show subpopulations

Gnomad4 AFR exome

AF:

0.00186

Gnomad4 AMR exome

AF:

0.000229

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:

0.00000119

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.000615

AC:

AN:

112191

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

AN XY:

34357

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.000283

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:

0.0000672

Hom.:

Bravo

AF:

0.000623

ESP6500AA

AF:

0.00261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000181

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2192A>G (p.D731G) alteration is located in exon 1 (coding exon 1) of the FAM47A gene. This alteration results from a A to G substitution at nucleotide position 2192, causing the aspartic acid (D) at amino acid position 731 to be replaced by a glycine (G). 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

Pathogenic

0.60

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.098

T;.

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-6.3

D;.

REVEL

Benign

0.042

Sift

Uncertain

0.023

D;.

Sift4G

Uncertain

0.010

D;D

Polyphen

1.0

D;.

Vest4

0.13

MVP

0.15

MPC

0.88

ClinPred

0.14

GERP RS

1.2

Varity_R

0.26

gMVP

0.064

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