20-3745920-G-T

Variant names:

• chr20-3745920-G-T
• NM_052970.5:c.564G>T
• HSPA12B p.Leu188Leu

Variant summary

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

The NM_001197327.2(HSPA12B):​c.561G>T​(p.Leu187Leu) variant causes a splice region, 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. 1/1 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)
• Consequence: HSPA12B NM_001197327.2 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• 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: 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=-0.47).
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197327.2. 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
	HSPA12B	NM_052970.5	MANE Select	c.564G>T	p.Leu188Leu	synonymous	Exon 7 of 13	NP_443202.3
	HSPA12B	NM_001197327.2		c.561G>T	p.Leu187Leu	splice_region synonymous	Exon 7 of 13	NP_001184256.1	B7ZLP2
	HSPA12B	NM_001318322.2		c.306G>T	p.Leu102Leu	synonymous	Exon 6 of 12	NP_001305251.1	Q5JX83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA12B	ENST00000254963.7	TSL:1 MANE Select	c.564G>T	p.Leu188Leu	synonymous	Exon 7 of 13	ENSP00000254963.2	Q96MM6
	HSPA12B	ENST00000399701.1	TSL:1	c.306G>T	p.Leu102Leu	synonymous	Exon 6 of 12	ENSP00000382608.1	Q5JX83
	HSPA12B	ENST00000969453.1		c.586G>T	p.Glu196*	stop_gained	Exon 7 of 12	ENSP00000639512.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.8
DANN	Benign	0.70
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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: chr20-3726567; COSMIC: COSV54767119;