rs204468

chr19-44987378-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001294.4(CLPTM1):c.993T>C(p.Gly331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,613,712 control chromosomes in the GnomAD database, including 303,703 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (22506 hom., cov: 34)
  • Exomes 𝑓: 0.62 (281197 hom.)
• Consequence: CLPTM1 NM_001294.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.05

Genes affected

CLPTM1 (HGNC:2087): (CLPTM1 regulator of GABA type A receptor forward trafficking) Predicted to be involved in regulation of T cell differentiation in thymus. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-8.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLPTM1	NM_001294.4	c.993T>C	p.Gly331=	synonymous_variant	8/14	ENST00000337392.10
CLPTM1	NM_001282175.2	c.951T>C	p.Gly317=	synonymous_variant	8/14
CLPTM1	NM_001282176.2	c.687T>C	p.Gly229=	synonymous_variant	8/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLPTM1	ENST00000337392.10	c.993T>C	p.Gly331=	synonymous_variant	8/14	1	NM_001294.4	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80084 AN: 152038 Hom.: 22494 Cov.: 34

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.536

GnomAD3 exomes AF: 0.568 AC: 142622 AN: 251188 Hom.: 41928 AF XY: 0.582 AC XY: 79055 AN XY: 135802

Gnomad AFR exome AF: 0.331

Gnomad AMR exome AF: 0.433

Gnomad ASJ exome AF: 0.602

Gnomad EAS exome AF: 0.449

Gnomad SAS exome AF: 0.642

Gnomad FIN exome AF: 0.583

Gnomad NFE exome AF: 0.635

Gnomad OTH exome AF: 0.587

GnomAD4 exome AF: 0.616 AC: 900323 AN: 1461556 Hom.: 281197 Cov.: 58 AF XY: 0.618 AC XY: 449370 AN XY: 727070

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.439

Gnomad4 ASJ exome AF: 0.605

Gnomad4 EAS exome AF: 0.428

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.640

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.527 AC: 80120 AN: 152156 Hom.: 22506 Cov.: 34 AF XY: 0.526 AC XY: 39103 AN XY: 74386

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.535

Alfa AF: 0.608 Hom.: 40757

Bravo AF: 0.508

Asia WGS AF: 0.495 AC: 1722 AN: 3478

EpiCase AF: 0.630

EpiControl AF: 0.626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.11
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs204468; hg19: chr19-45490636; COSMIC: COSV61611028; COSMIC: COSV61611028;