Genetic Variant NM_152785.5:c.238T>C (chr3-112123754-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152785.5(GCSAM):c.238T>C(p.Tyr80His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GCSAM
NM_152785.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.886

Variant links:

Genes affected

GCSAM (HGNC:20253): (germinal center associated signaling and motility) This gene encodes a protein which may function in signal transduction pathways and whose expression is elevated in germinal cell lymphomas. It contains a putative PDZ-interacting domain, an immunoreceptor tyrosine-based activation motif (ITAM), and two putative SH2 binding sites. In B cells, its expression is specifically induced by interleukin-4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

GCSAM links:

C3orf52 (HGNC:26255): (chromosome 3 open reading frame 52) Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C3orf52 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.070654154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCSAM	NM_152785.5 link	c.238T>C	p.Tyr80His	missense_variant	Exon 6 of 6	ENST00000308910.9	NP_689998.1	Q8N6F7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCSAM	ENST00000308910.9 link	c.238T>C	p.Tyr80His	missense_variant	Exon 6 of 6	1	NM_152785.5	ENSP00000309487.4		Q8N6F7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249768

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134840

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:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460680

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726482

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:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.13

T;.;.;.;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.078

M_CAP

Benign

0.0048

MetaRNN

Benign

0.071

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.85

N;N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.25

T;T;T;T;T

Sift4G

Benign

0.62

T;T;T;.;.

Polyphen

0.023

B;.;.;.;.

Vest4

0.067

MutPred

0.29

Gain of disorder (P = 0.0317);.;.;.;.;

MVP

0.076

MPC

0.68

ClinPred

0.12

GERP RS

0.78

Varity_R

0.039

gMVP

0.039

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over