chr19-44987378-T-C

Variant names:

• chr19-44987378-T-C
• rs204468
• NM_001294.4:c.993T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001294.4(CLPTM1):​c.993T>C​(p.Gly331Gly) 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
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001294.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1	NM_001294.4	MANE Select	c.993T>C	p.Gly331Gly	synonymous	Exon 8 of 14	NP_001285.1
	CLPTM1	NM_001282175.2		c.951T>C	p.Gly317Gly	synonymous	Exon 8 of 14	NP_001269104.1
	CLPTM1	NM_001282176.2		c.687T>C	p.Gly229Gly	synonymous	Exon 8 of 14	NP_001269105.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1	ENST00000337392.10	TSL:1 MANE Select	c.993T>C	p.Gly331Gly	synonymous	Exon 8 of 14	ENSP00000336994.4
	CLPTM1	ENST00000588855.5	TSL:1	n.1038T>C		non_coding_transcript_exon	Exon 8 of 8
	CLPTM1	ENST00000541297.6	TSL:2	c.951T>C	p.Gly317Gly	synonymous	Exon 8 of 14	ENSP00000442011.1

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

GnomAD2 exomes AF: 0.568 AC: 142622 AN: 251188 AF XY: 0.582

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 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

African (AFR) AF: 0.336 AC: 11252 AN: 33474

American (AMR) AF: 0.439 AC: 19609 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 15802 AN: 26134

East Asian (EAS) AF: 0.428 AC: 16970 AN: 39690

South Asian (SAS) AF: 0.637 AC: 54966 AN: 86246

European-Finnish (FIN) AF: 0.587 AC: 31305 AN: 53294

Middle Eastern (MID) AF: 0.601 AC: 3468 AN: 5766

European-Non Finnish (NFE) AF: 0.640 AC: 711240 AN: 1111862

Other (OTH) AF: 0.591 AC: 35711 AN: 60384

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

African (AFR) AF: 0.341 AC: 14140 AN: 41520

American (AMR) AF: 0.488 AC: 7465 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2125 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2232 AN: 5166

South Asian (SAS) AF: 0.611 AC: 2950 AN: 4826

European-Finnish (FIN) AF: 0.581 AC: 6145 AN: 10572

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43172 AN: 67990

Other (OTH) AF: 0.535 AC: 1130 AN: 2114

Alfa AF: 0.586 Hom.: 66240

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.11
DANN	Benign	0.41
PhyloP100		-8.0
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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