20-3745918-CTG-GTA

Variant names:

• chr20-3745918-CTG-GTA
• NM_052970.5:c.562_564delCTGinsGTA
• HSPA12B p.Leu188Val

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_052970.5(HSPA12B):​c.562_564delCTGinsGTA​(p.Leu188Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSPA12B NM_052970.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.56
• Publications: 0 publications found

Genes affected

HSPA12B (HGNC:16193): (heat shock protein family A (Hsp70) member 12B) The protein encoded by this gene contains an atypical heat shock protein 70 (Hsp70) ATPase domain and is therefore a distant member of the mammalian Hsp70 family. This gene may be involved in susceptibility to atherosclerosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052970.5. 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
	HSPA12B	NM_052970.5	MANE Select	c.562_564delCTGinsGTA	p.Leu188Val	missense	N/A	NP_443202.3
	HSPA12B	NM_001318322.2		c.304_306delCTGinsGTA	p.Leu102Val	missense	N/A	NP_001305251.1	Q5JX83
	HSPA12B	NM_001197327.2		c.559_561delCTGinsGTA	p.Leu187Val	missense splice_region	N/A	NP_001184256.1	B7ZLP2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA12B	ENST00000254963.7	TSL:1 MANE Select	c.562_564delCTGinsGTA	p.Leu188Val	missense	N/A	ENSP00000254963.2	Q96MM6
	HSPA12B	ENST00000399701.1	TSL:1	c.304_306delCTGinsGTA	p.Leu102Val	missense	N/A	ENSP00000382608.1	Q5JX83
	HSPA12B	ENST00000887993.1		c.562_564delCTGinsGTA	p.Leu188Val	missense	N/A	ENSP00000558052.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-3726565;