chr19-44987312-A-C

Variant names:

• chr19-44987312-A-C
• rs3786505
• NM_001294.4:c.927A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001294.4(CLPTM1):​c.927A>C​(p.Pro309Pro) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 35)
• Consequence: CLPTM1 NM_001294.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.33
• Publications: 25 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-5.33 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1	NM_001294.4	MANE Select	c.927A>C	p.Pro309Pro	synonymous	Exon 8 of 14	NP_001285.1
	CLPTM1	NM_001282175.2		c.885A>C	p.Pro295Pro	synonymous	Exon 8 of 14	NP_001269104.1
	CLPTM1	NM_001282176.2		c.621A>C	p.Pro207Pro	synonymous	Exon 8 of 14	NP_001269105.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1	ENST00000337392.10	TSL:1 MANE Select	c.927A>C	p.Pro309Pro	synonymous	Exon 8 of 14	ENSP00000336994.4
	CLPTM1	ENST00000588855.5	TSL:1	n.972A>C		non_coding_transcript_exon	Exon 8 of 8
	CLPTM1	ENST00000541297.6	TSL:2	c.885A>C	p.Pro295Pro	synonymous	Exon 8 of 14	ENSP00000442011.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 8800

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.079
DANN	Benign	0.50
PhyloP100		-5.3

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: rs3786505; hg19: chr19-45490570;