rs760499739

Variant names:

• chr19-44955423-G-A
• rs760499739
• NM_001294.4:c.28G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-44955423-G-A
• chr19-44955423-G-C
• chr19-44955423-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001294.4(CLPTM1):​c.28G>A​(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,341,234 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: CLPTM1 NM_001294.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17039385).
• BS2: High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPTM1	NM_001294.4	c.28G>A	p.Ala10Thr	missense_variant	Exon 1 of 14	ENST00000337392.10	NP_001285.1
CLPTM1	NM_001282175.2	c.30+338G>A		intron_variant	Intron 1 of 13		NP_001269104.1
CLPTM1	NM_001282176.2	c.-235+722G>A		intron_variant	Intron 1 of 13		NP_001269105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPTM1	ENST00000337392.10	c.28G>A	p.Ala10Thr	missense_variant	Exon 1 of 14	1	NM_001294.4	ENSP00000336994.4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000193 AC: 23 AN: 1188946 Hom.: 0 Cov.: 30 AF XY: 0.0000192 AC XY: 11 AN XY: 571894

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000353

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000279

Gnomad4 NFE exome AF: 0.0000204

Gnomad4 OTH exome AF: 0.0000206

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152288 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74462

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.66	T;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-0.34	N;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.17	N;.
REVEL	Benign	0.096
Sift	Benign	0.44	T;.
Sift4G	Benign	0.27	T;T
Polyphen		0.98	D;.
Vest4		0.13
MutPred		0.12		Gain of glycosylation at A10 (P = 0.0144);Gain of glycosylation at A10 (P = 0.0144);
MVP		0.36
MPC		1.6
ClinPred		0.94	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.37

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: rs760499739; hg19: chr19-45458680;