NM_030782.5:c.1174A>G

Variant names:

• chr5-1324786-T-C
• rs1561231523
• NM_030782.5:c.1174A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030782.5(CLPTM1L):​c.1174A>G​(p.Lys392Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CLPTM1L NM_030782.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19127741).

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.1174A>G	p.Lys392Glu	missense	Exon 11 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.1174A>G	p.Lys392Glu	missense	Exon 11 of 17	ENSP00000313854.5	Q96KA5-1
	CLPTM1L	ENST00000507807.3	TSL:1	c.667A>G	p.Lys223Glu	missense	Exon 8 of 14	ENSP00000423321.1	G5E9Z2
	CLPTM1L	ENST00000966757.1		c.1378A>G	p.Lys460Glu	missense	Exon 12 of 18	ENSP00000636816.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461826 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.34
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.92	L
PhyloP100		4.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.050
Sift	Benign	0.28	T
Sift4G	Benign	0.96	T
Polyphen		0.0010	B
Vest4		0.38
MutPred		0.45		Loss of ubiquitination at K392 (P = 6e-04)
MVP		0.29
MPC		0.46
ClinPred		0.38	T
GERP RS		4.0
Varity_R		0.11
gMVP		0.53
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1561231523; hg19: chr5-1324901;