rs1390106775

Variant names:

• chr19-44955419-C-A
• rs1390106775
• NM_001294.4:c.24C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-44955419-C-A
• chr19-44955419-C-G
• chr19-44955419-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001294.4(CLPTM1):​c.24C>A​(p.Asp8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,168,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CLPTM1 NM_001294.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.82
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24954373).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

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.24C>A	p.Asp8Glu	missense	Exon 1 of 14	NP_001285.1	A0A0S2Z3H2
	CLPTM1	NM_001282175.2		c.30+334C>A		intron	N/A	NP_001269104.1	O96005-4
	CLPTM1	NM_001282176.2		c.-235+718C>A		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.24C>A	p.Asp8Glu	missense	Exon 1 of 14	ENSP00000336994.4	O96005-1
	CLPTM1	ENST00000588855.5	TSL:1	n.117+718C>A		intron	N/A
	CLPTM1	ENST00000870268.1		c.24C>A	p.Asp8Glu	missense	Exon 1 of 15	ENSP00000540327.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000120 AC: 14 AN: 1168070 Hom.: 0 Cov.: 30 AF XY: 0.0000142 AC XY: 8 AN XY: 562024

African (AFR) AF: 0.00 AC: 0 AN: 22976

American (AMR) AF: 0.00 AC: 0 AN: 10424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15654

East Asian (EAS) AF: 0.00 AC: 0 AN: 28072

South Asian (SAS) AF: 0.00 AC: 0 AN: 41174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3196

European-Non Finnish (NFE) AF: 0.0000145 AC: 14 AN: 964954

Other (OTH) AF: 0.00 AC: 0 AN: 47722

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.071
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.12
Sift	Benign	0.33	T
Sift4G	Benign	0.96	T
Polyphen		0.98	D
Vest4		0.22
MutPred		0.085		Gain of helix (P = 0.0325)
MVP		0.50
MPC		1.6
ClinPred		0.79	D
GERP RS		3.4
PromoterAI		0.23	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.36
Mutation Taster		=89/11	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: rs1390106775; hg19: chr19-45458676;