Variant chr1-247574351-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145278.5(GCSAML):c.377A>G(p.Glu126Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

GCSAML
NM_145278.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

GCSAML (HGNC:29583): (germinal center associated signaling and motility like) This gene encodes a protein thought to be a signaling molecule associated with germinal centers, the sites of proliferation and differentiation of mature B lymphocytes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

GCSAML links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05285272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCSAML	NM_145278.5 linkuse as main transcript	c.377A>G	p.Glu126Gly	missense_variant	5/5	ENST00000366488.5
LOC102724446	XR_426948.4 linkuse as main transcript	n.226-8400T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCSAML	ENST00000366488.5 linkuse as main transcript	c.377A>G	p.Glu126Gly	missense_variant	5/5	1	NM_145278.5	P1	Q5JQS6-1
	ENST00000435333.5 linkuse as main transcript	n.226-8400T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000387

AC:

AN:

250836

Hom.:

AF XY:

0.000347

AC XY:

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000879

Gnomad NFE exome

AF:

0.000627

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.000268

AC:

392

AN:

1461774

Hom.:

Cov.:

AF XY:

0.000264

AC XY:

192

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00127

Gnomad4 NFE exome

AF:

0.000274

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000138

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000519

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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

Mar 06, 2023

The c.377A>G (p.E126G) alteration is located in exon 5 (coding exon 5) of the GCSAML gene. This alteration results from a A to G substitution at nucleotide position 377, causing the glutamic acid (E) at amino acid position 126 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

Benign

0.22

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T;T;.;.;T;T;T

Eigen

Benign

-0.039

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.66

.;T;.;.;T;.;T;.

M_CAP

Benign

0.0018

MetaRNN

Benign

0.053

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.4

.;M;.;.;.;.;.;M

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-5.9

D;.;D;D;D;D;.;D

REVEL

Benign

0.11

Sift

Uncertain

0.0030

D;.;D;D;D;D;.;D

Sift4G

Uncertain

0.019

D;D;D;D;D;D;D;D

Polyphen

0.93

.;P;.;.;.;.;.;P

Vest4

0.20

MVP

0.29

MPC

0.16

ClinPred

0.16

GERP RS

3.9

Varity_R

0.41

gMVP

0.035

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