Variant chrX-154444311-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_004699.4(FAM50A):c.76G>A(p.Glu26Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000233 in 1,115,505 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 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 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000024 ( 0 hom. 10 hem. )

Consequence

FAM50A
NM_004699.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

Variant links:

Genes affected

FAM50A (HGNC:18786): (family with sequence similarity 50 member A) This gene belongs to the FAM50 family. The encoded protein is highly conserved in length and sequence across different species. It is a basic protein containing a nuclear localization signal, and may function as a DNA-binding protein or a transcriptional factor. [provided by RefSeq, Sep 2009]

FAM50A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33883965).

BS2

High Hemizygotes in GnomAdExome4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM50A	NM_004699.4 linkuse as main transcript	c.76G>A	p.Glu26Lys	missense_variant	1/13	ENST00000393600.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAM50A	ENST00000393600.8 linkuse as main transcript	c.76G>A	p.Glu26Lys	missense_variant	1/13	1	NM_004699.4	P1
FAM50A	ENST00000464419.5 linkuse as main transcript	n.157G>A		non_coding_transcript_exon_variant	1/12	5
FAM50A	ENST00000481619.5 linkuse as main transcript	n.64G>A		non_coding_transcript_exon_variant	1/7	2

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112286

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34682

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:

0.0000189

Gnomad OTH

AF:

0.000661

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1003219

Hom.:

Cov.:

AF XY:

0.0000315

AC XY:

AN XY:

317371

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000290

Gnomad4 OTH exome

AF:

0.0000243

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112286

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34682

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:

0.0000189

Gnomad4 OTH

AF:

0.000661

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.17

Sift

Benign

0.055

Sift4G

Benign

0.46

Polyphen

0.94

Vest4

0.35

MutPred

0.22

Gain of methylation at E26 (P = 0.0123);

MVP

0.40

MPC

1.5

ClinPred

0.95

GERP RS

2.3

Varity_R

0.53

gMVP

0.91

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