19-44987312-A-G

Position:

• chr19-44987312-A-G

Variant summary

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

The NM_001294.4(CLPTM1):​c.927A>G​(p.Pro309=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,614,028 control chromosomes in the GnomAD database, including 95,748 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 0.39 (11929 hom., cov: 35)
  • Exomes 𝑓: 0.33 (83819 hom.)
• Consequence: CLPTM1 NM_001294.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.33

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=-0.88).
• BP7: Synonymous conserved (PhyloP=-5.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLPTM1	NM_001294.4	c.927A>G	p.Pro309=	synonymous_variant	8/14	ENST00000337392.10
CLPTM1	NM_001282175.2	c.885A>G	p.Pro295=	synonymous_variant	8/14
CLPTM1	NM_001282176.2	c.621A>G	p.Pro207=	synonymous_variant	8/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLPTM1	ENST00000337392.10	c.927A>G	p.Pro309=	synonymous_variant	8/14	1	NM_001294.4	P1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58857 AN: 152056 Hom.: 11905 Cov.: 35

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.387

GnomAD3 exomes AF: 0.371 AC: 93177 AN: 251422 Hom.: 18002 AF XY: 0.361 AC XY: 49084 AN XY: 135892

Gnomad AFR exome AF: 0.479

Gnomad AMR exome AF: 0.455

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.482

Gnomad SAS exome AF: 0.307

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.326

Gnomad OTH exome AF: 0.358

GnomAD4 exome AF: 0.335 AC: 489197 AN: 1461854 Hom.: 83819 Cov.: 56 AF XY: 0.333 AC XY: 242378 AN XY: 727232

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.387 AC: 58934 AN: 152174 Hom.: 11929 Cov.: 35 AF XY: 0.389 AC XY: 28969 AN XY: 74418

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.389

Alfa AF: 0.342 Hom.: 7706

Bravo AF: 0.396

Asia WGS AF: 0.425 AC: 1479 AN: 3478

EpiCase AF: 0.328

EpiControl AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.081
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs3786505; hg19: chr19-45490570; COSMIC: COSV61611380; COSMIC: COSV61611380;