5-1325771-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030782.5(CLPTM1L):c.1126G>A(p.Gly376Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLPTM1L NM_030782.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.28

Genes affected

CLPTM1L (HGNC:24308): (CLPTM1 like) The protein encoded by this gene is a membrane protein whose overexpression in cisplatin-sensitive cells causes apoptosis. Polymorphisms in this gene have been reported to increase susceptibility to several cancers, including lung, pancreatic, and breast cancers. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35797977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLPTM1L	NM_030782.5	c.1126G>A	p.Gly376Ser	missense_variant	10/17	ENST00000320895.10
CLPTM1L	XM_011514144.3	c.1123G>A	p.Gly375Ser	missense_variant	10/17
CLPTM1L	XM_024446222.2	c.592G>A	p.Gly198Ser	missense_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.1126G>A	p.Gly376Ser	missense_variant	10/17	1	NM_030782.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2022

The c.1126G>A (p.G376S) alteration is located in exon 10 (coding exon 10) of the CLPTM1L gene. This alteration results from a G to A substitution at nucleotide position 1126, causing the glycine (G) at amino acid position 376 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	22
Dann	Benign	0.90
DEOGEN2	Benign	0.20	T;.;.
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.75	T;.;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.5	L;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.5	D;N;.
REVEL	Benign	0.17
Sift	Benign	0.17	T;T;.
Sift4G	Benign	0.23	T;T;T
Polyphen		0.25	B;B;B
Vest4		0.47
MutPred		0.62		Loss of sheet (P = 0.0228);.;.;
MVP		0.48
MPC		0.37
ClinPred		0.75	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-1325886;