Genetic Variant NM_152785.5:c.478T>C (chr3-112123514-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152785.5(GCSAM):c.478T>C(p.Phe160Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GCSAM
NM_152785.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.503

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hypotrichosis 15
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

C3orf52 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042280525).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152785.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GCSAM	NM_152785.5	MANE Select	c.478T>C	p.Phe160Leu	missense	Exon 6 of 6	NP_689998.1	Q8N6F7-1
GCSAM	NM_001190259.2		c.484T>C	p.Phe162Leu	missense	Exon 6 of 6	NP_001177188.1	Q8N6F7-2
GCSAM	NM_001190260.2		c.433T>C	p.Phe145Leu	missense	Exon 5 of 5	NP_001177189.1	Q8N6F7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GCSAM	ENST00000308910.9	TSL:1 MANE Select	c.478T>C	p.Phe160Leu	missense	Exon 6 of 6	ENSP00000309487.4	Q8N6F7-1
C3orf52	ENST00000467942.2	TSL:1	n.950+3952A>G		intron	N/A
GCSAM	ENST00000484193.5	TSL:2	c.484T>C	p.Phe162Leu	missense	Exon 6 of 6	ENSP00000419485.1	Q8N6F7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.12

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.060

M_CAP

Benign

0.0026

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.50

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.60

REVEL

Benign

0.046

Sift

Benign

0.12

Sift4G

Benign

0.16

Polyphen

0.13

Vest4

0.074

MutPred

0.062

Gain of relative solvent accessibility (P = 0.1259)

MVP

0.067

MPC

0.27

ClinPred

0.045

GERP RS

0.025

Varity_R

0.035

gMVP

0.052

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over