NM_001294.4:c.40G>C

Variant names:

• chr19-44955435-G-C
• rs962978211
• NM_001294.4:c.40G>C

Variant summary

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

The NM_001294.4(CLPTM1):​c.40G>C​(p.Val14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000846 in 1,181,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V14M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: CLPTM1 NM_001294.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56
• Publications: 0 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: 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=0.20329848).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1	NM_001294.4	MANE Select	c.40G>C	p.Val14Leu	missense	Exon 1 of 14	NP_001285.1	A0A0S2Z3H2
	CLPTM1	NM_001282175.2		c.30+350G>C		intron	N/A	NP_001269104.1	O96005-4
	CLPTM1	NM_001282176.2		c.-235+734G>C		intron	N/A	NP_001269105.1	O96005-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1	ENST00000337392.10	TSL:1 MANE Select	c.40G>C	p.Val14Leu	missense	Exon 1 of 14	ENSP00000336994.4	O96005-1
	CLPTM1	ENST00000588855.5	TSL:1	n.117+734G>C		intron	N/A
	CLPTM1	ENST00000870268.1		c.40G>C	p.Val14Leu	missense	Exon 1 of 15	ENSP00000540327.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.46e-7 AC: 1 AN: 1181650 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 567394

African (AFR) AF: 0.00 AC: 0 AN: 23280

American (AMR) AF: 0.00 AC: 0 AN: 10178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15896

East Asian (EAS) AF: 0.00 AC: 0 AN: 28150

South Asian (SAS) AF: 0.00 AC: 0 AN: 39306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3290

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 976824

Other (OTH) AF: 0.00 AC: 0 AN: 48334

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.064
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.6
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.13
Sift	Benign	0.28	T
Sift4G	Benign	0.80	T
Polyphen		0.22	B
Vest4		0.21
MutPred		0.18		Loss of sheet (P = 0.0025)
MVP		0.24
MPC		1.3
ClinPred		0.81	D
GERP RS		3.4
PromoterAI		-0.19	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.39
Mutation Taster		=83/17	polymorphism

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: rs962978211; hg19: chr19-45458692;