19-44955448-G-T

Variant names:

• chr19-44955448-G-T
• rs980948842
• NM_001294.4:c.53G>T

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.53G>T​(p.Gly18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000003 in 1,334,830 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. 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. G18E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: CLPTM1 NM_001294.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• 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=0.1757794).

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.53G>T	p.Gly18Val	missense	Exon 1 of 14	NP_001285.1	A0A0S2Z3H2
	CLPTM1	NM_001282175.2		c.30+363G>T		intron	N/A	NP_001269104.1	O96005-4
	CLPTM1	NM_001282176.2		c.-235+747G>T		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.53G>T	p.Gly18Val	missense	Exon 1 of 14	ENSP00000336994.4	O96005-1
	CLPTM1	ENST00000588855.5	TSL:1	n.117+747G>T		intron	N/A
	CLPTM1	ENST00000870268.1		c.53G>T	p.Gly18Val	missense	Exon 1 of 15	ENSP00000540327.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152250 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: 0.00318

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000254 AC: 3 AN: 1182466 Hom.: 0 Cov.: 31 AF XY: 0.00000176 AC XY: 1 AN XY: 567544

African (AFR) AF: 0.00 AC: 0 AN: 23306

American (AMR) AF: 0.00 AC: 0 AN: 10204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15912

East Asian (EAS) AF: 0.00 AC: 0 AN: 28122

South Asian (SAS) AF: 0.00 AC: 0 AN: 38780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3328

European-Non Finnish (NFE) AF: 0.00000307 AC: 3 AN: 977344

Other (OTH) AF: 0.00 AC: 0 AN: 48346

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152364 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74504

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.62	T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.1
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.080
Sift	Benign	0.16	T
Sift4G	Uncertain	0.027	D
Polyphen		0.35	B
Vest4		0.32
MutPred		0.28		Gain of sheet (P = 0.0061)
MVP		0.25
MPC		0.93
ClinPred		0.41	T
GERP RS		2.3
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.31
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs980948842; hg19: chr19-45458705;