5-1325771-C-T

Variant names:

• chr5-1325771-C-T
• NM_030782.5:c.1126G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030782.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1L	NM_030782.5	MANE Select	c.1126G>A	p.Gly376Ser	missense	Exon 10 of 17	NP_110409.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1L	ENST00000320895.10	TSL:1 MANE Select	c.1126G>A	p.Gly376Ser	missense	Exon 10 of 17	ENSP00000313854.5	Q96KA5-1
	CLPTM1L	ENST00000507807.3	TSL:1	c.619G>A	p.Gly207Ser	missense	Exon 7 of 14	ENSP00000423321.1	G5E9Z2
	CLPTM1L	ENST00000966757.1		c.1126G>A	p.Gly376Ser	missense	Exon 10 of 18	ENSP00000636816.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.3
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.17
Sift	Benign	0.17	T
Sift4G	Benign	0.23	T
Polyphen		0.25	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
Mutation Taster		=31/69	disease causing

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

hg19: chr5-1325886;