NM_001294.4:c.927A>G

Variant names:

• chr19-44987312-A-G
• rs3786505
• NM_001294.4:c.927A>G

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.927A>G​(p.Pro309Pro) 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
• Publications: 25 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=-0.88).
• 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.

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.927A>G	p.Pro309Pro	synonymous	Exon 8 of 14	NP_001285.1
	CLPTM1	NM_001282175.2		c.885A>G	p.Pro295Pro	synonymous	Exon 8 of 14	NP_001269104.1
	CLPTM1	NM_001282176.2		c.621A>G	p.Pro207Pro	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.927A>G	p.Pro309Pro	synonymous	Exon 8 of 14	ENSP00000336994.4
	CLPTM1	ENST00000588855.5	TSL:1	n.972A>G		non_coding_transcript_exon	Exon 8 of 8
	CLPTM1	ENST00000541297.6	TSL:2	c.885A>G	p.Pro295Pro	synonymous	Exon 8 of 14	ENSP00000442011.1

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

GnomAD2 exomes AF: 0.371 AC: 93177 AN: 251422 AF XY: 0.361

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 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

African (AFR) AF: 0.470 AC: 15735 AN: 33480

American (AMR) AF: 0.450 AC: 20139 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 9766 AN: 26136

East Asian (EAS) AF: 0.462 AC: 18342 AN: 39700

South Asian (SAS) AF: 0.314 AC: 27092 AN: 86258

European-Finnish (FIN) AF: 0.382 AC: 20413 AN: 53408

Middle Eastern (MID) AF: 0.350 AC: 2019 AN: 5768

European-Non Finnish (NFE) AF: 0.319 AC: 354321 AN: 1111986

Other (OTH) AF: 0.354 AC: 21370 AN: 60396

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

African (AFR) AF: 0.479 AC: 19887 AN: 41518

American (AMR) AF: 0.409 AC: 6256 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1263 AN: 3468

East Asian (EAS) AF: 0.495 AC: 2557 AN: 5168

South Asian (SAS) AF: 0.337 AC: 1628 AN: 4828

European-Finnish (FIN) AF: 0.387 AC: 4095 AN: 10590

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22075 AN: 67996

Other (OTH) AF: 0.389 AC: 823 AN: 2114

Alfa AF: 0.344 Hom.: 8800

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.081
DANN	Benign	0.48
PhyloP100		-5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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