11-123061415-C-A

Variant names:

• chr11-123061415-C-A
• rs10892958
• NM_006597.6:c.-5-86G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006597.6(HSPA8):​c.-5-86G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000677 in 886,766 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: HSPA8 NM_006597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.-5-86G>T		intron	N/A	NP_006588.1	P11142-1
	HSPA8	NM_153201.4		c.-5-86G>T		intron	N/A	NP_694881.1	P11142-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.-5-86G>T		intron	N/A	ENSP00000432083.1	P11142-1
	HSPA8	ENST00000453788.6	TSL:1	c.-5-86G>T		intron	N/A	ENSP00000404372.2	P11142-2
	HSPA8	ENST00000527983.5	TSL:1	n.145-86G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000677 AC: 6 AN: 886766 Hom.: 0 Cov.: 11 AF XY: 0.00000439 AC XY: 2 AN XY: 455508

African (AFR) AF: 0.00 AC: 0 AN: 21924

American (AMR) AF: 0.00 AC: 0 AN: 33462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20718

East Asian (EAS) AF: 0.00 AC: 0 AN: 33550

South Asian (SAS) AF: 0.0000447 AC: 3 AN: 67160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43794

Middle Eastern (MID) AF: 0.000219 AC: 1 AN: 4568

European-Non Finnish (NFE) AF: 0.00000161 AC: 1 AN: 620452

Other (OTH) AF: 0.0000243 AC: 1 AN: 41138

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.92
DANN	Benign	0.49
PhyloP100		-1.2
PromoterAI		-0.012	Neutral

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: rs10892958; hg19: chr11-122932123;