19-44961958-C-T

Variant names:

• chr19-44961958-C-T
• rs768475727
• NM_001294.4:c.73-5C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_001294.4(CLPTM1):​c.73-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,444,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: CLPTM1 NM_001294.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001030
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BS2: High AC in GnomAdExome4 at 5 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.73-5C>T		splice_region intron	N/A	NP_001285.1	A0A0S2Z3H2
	CLPTM1	NM_001282175.2		c.31-5C>T		splice_region intron	N/A	NP_001269104.1	O96005-4
	CLPTM1	NM_001282176.2		c.-234-5C>T		splice_region 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.73-5C>T		splice_region intron	N/A	ENSP00000336994.4	O96005-1
	CLPTM1	ENST00000588855.5	TSL:1	n.118-5C>T		splice_region intron	N/A
	CLPTM1	ENST00000870268.1		c.73-5C>T		splice_region intron	N/A	ENSP00000540327.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000852 AC: 2 AN: 234800 AF XY: 0.00000782

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000477

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1444630 Hom.: 0 Cov.: 29 AF XY: 0.00000556 AC XY: 4 AN XY: 718784

African (AFR) AF: 0.00 AC: 0 AN: 32628

American (AMR) AF: 0.00 AC: 0 AN: 41020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25432

East Asian (EAS) AF: 0.00 AC: 0 AN: 39008

South Asian (SAS) AF: 0.00 AC: 0 AN: 83924

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104554

Other (OTH) AF: 0.0000336 AC: 2 AN: 59556

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.6
DANN	Benign	0.84
PhyloP100		-0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.036
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: rs768475727; hg19: chr19-45465215;