HSPA8 p.Val335Val

Variant names:

• chr11-123059587-G-G
• NM_006597.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr11-123059588--
• chr11-123059588-G-A
• chr11-123059588-G-T
• chr11-123059588-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006597.6(HSPA8):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSPA8 NM_006597.6 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

Genes affected

HSPA8 (HGNC:5241): (heat shock protein family A (Hsp70) member 8) This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

SNORD14C (HGNC:30352): (small nucleolar RNA, C/D box 14C)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006597.6. 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
	HSPA8	NM_006597.6	MANE Select	c.		exon_region	Exon 5 of 9	NP_006588.1	P11142-1
	HSPA8	NM_153201.4		c.		exon_region	Exon 5 of 8	NP_694881.1	P11142-2
	SNORD14C	NR_001453.2		n.		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.		exon_region	Exon 5 of 9	ENSP00000432083.1	P11142-1
	HSPA8	ENST00000227378.7	TSL:1	c.		exon_region	Exon 4 of 8	ENSP00000227378.3	P11142-1
	HSPA8	ENST00000453788.6	TSL:1	c.		exon_region	Exon 5 of 8	ENSP00000404372.2	P11142-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

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: chr11-122930295;