chr19-44955419-C-G

Variant names:

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

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.24C>G​(p.Asp8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000227 in 1,319,796 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000017 (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: 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=0.24769422).

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

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151722 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000171 AC: 2 AN: 1168074 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 562026

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: 0.00000207 AC: 2 AN: 964958

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

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151722 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74098

African (AFR) AF: 0.00 AC: 0 AN: 41286

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67912

Other (OTH) AF: 0.00 AC: 0 AN: 2088

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	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.48	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	0.17
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		0.72	D
GERP RS		3.4
PromoterAI		-0.15	Neutral
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;