3-112125234-G-C

Variant names:

• chr3-112125234-G-C
• rs147855189
• NM_152785.5:c.211C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152785.5(GCSAM):​c.211C>G​(p.Pro71Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,424,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P71T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GCSAM NM_152785.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07219136).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCSAM	NM_152785.5	MANE Select	c.211C>G	p.Pro71Ala	missense	Exon 5 of 6	NP_689998.1	Q8N6F7-1
	GCSAM	NM_001190259.2		c.217C>G	p.Pro73Ala	missense	Exon 5 of 6	NP_001177188.1	Q8N6F7-2
	GCSAM	NM_001190260.2		c.166C>G	p.Pro56Ala	missense	Exon 4 of 5	NP_001177189.1	Q8N6F7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCSAM	ENST00000308910.9	TSL:1 MANE Select	c.211C>G	p.Pro71Ala	missense	Exon 5 of 6	ENSP00000309487.4	Q8N6F7-1
	C3orf52	ENST00000467942.2	TSL:1	n.951-2999G>C		intron	N/A
	GCSAM	ENST00000484193.5	TSL:2	c.217C>G	p.Pro73Ala	missense	Exon 5 of 6	ENSP00000419485.1	Q8N6F7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1424168 Hom.: 0 Cov.: 25 AF XY: 0.00000141 AC XY: 1 AN XY: 711092

African (AFR) AF: 0.00 AC: 0 AN: 32604

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.00 AC: 0 AN: 85478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1077840

Other (OTH) AF: 0.00 AC: 0 AN: 59100

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.73
DEOGEN2	Uncertain	0.61	D
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.15	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.4
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.019
Sift	Benign	0.16	T
Sift4G	Uncertain	0.059	T
Polyphen		0.025	B
Vest4		0.42
MutPred		0.22		Loss of stability (P = 0.0652)
MVP		0.055
MPC		0.14
ClinPred		0.14	T
GERP RS		2.4
Varity_R		0.084
gMVP		0.027
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147855189; hg19: chr3-111844081; COSMIC: COSV58264593;