Genetic Variant FAM47A:p.Glu786Lys (chrX-34129923-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_203408.4(FAM47A):c.2356G>A(p.Glu786Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000092 in 1,195,653 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000083 ( 0 hom. 4 hem. )

Consequence

FAM47A
NM_203408.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.01

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=0.13006893).

BP6

Variant X-34129923-C-T is Benign according to our data. Variant chrX-34129923-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388985.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47A	NM_203408.4 link	c.2356G>A	p.Glu786Lys	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.2356G>A	p.Glu786Lys	missense_variant	Exon 1 of 1	6	NM_203408.4	ENSP00000345029.3		Q5JRC9

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112187

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34359

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000593

AC:

AN:

168629

Hom.:

AF XY:

0.00

AC XY:

AN XY:

56023

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000831

AC:

AN:

1083466

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

352550

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000194

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000440

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112187

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34359

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAM47A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-1.0

CADD

Benign

6.9

DANN

Benign

0.96

DEOGEN2

Benign

0.018

T;.

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.00097

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.3

N;.

REVEL

Benign

0.044

Sift

Benign

0.11

T;.

Sift4G

Benign

0.11

T;T

Polyphen

0.19

B;.

Vest4

0.071

MutPred

0.27

Gain of methylation at E786 (P = 0.0037);.;

MVP

0.043

MPC

0.26

ClinPred

0.090

GERP RS

1.3

Varity_R

0.078

gMVP

0.15

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