19-44973099-C-T

Variant names:

• chr19-44973099-C-T
• NM_001294.4:c.198C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_001282176.2(CLPTM1):​c.-109C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLPTM1 NM_001282176.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.86
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 19-44973099-C-T is Benign according to our data. Variant chr19-44973099-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3029011.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282176.2. 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.198C>T	p.Ile66Ile	synonymous	Exon 3 of 14	NP_001285.1	A0A0S2Z3H2
	CLPTM1	NM_001282176.2		c.-109C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 14	NP_001269105.1	O96005-3
	CLPTM1	NM_001282175.2		c.156C>T	p.Ile52Ile	synonymous	Exon 3 of 14	NP_001269104.1	O96005-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1	ENST00000337392.10	TSL:1 MANE Select	c.198C>T	p.Ile66Ile	synonymous	Exon 3 of 14	ENSP00000336994.4	O96005-1
	CLPTM1	ENST00000588855.5	TSL:1	n.243C>T		non_coding_transcript_exon	Exon 3 of 8
	CLPTM1	ENST00000546079.5	TSL:2	c.-109C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 14	ENSP00000443192.1	O96005-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CLPTM1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		1.9

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

hg19: chr19-45476356;