NM_006597.6:c.-5-86G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006597.6(HSPA8):​c.-5-86G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,037,656 control chromosomes in the GnomAD database, including 30,804 homozygotes. 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: 𝑓 0.28 (7122 hom., cov: 32)
  • Exomes 𝑓: 0.22 (23682 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

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>C		intron	N/A	NP_006588.1	P11142-1
	HSPA8	NM_153201.4		c.-5-86G>C		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>C		intron	N/A	ENSP00000432083.1	P11142-1
	HSPA8	ENST00000453788.6	TSL:1	c.-5-86G>C		intron	N/A	ENSP00000404372.2	P11142-2
	HSPA8	ENST00000527983.5	TSL:1	n.145-86G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42310 AN: 151954 Hom.: 7101 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.222 AC: 196753 AN: 885584 Hom.: 23682 Cov.: 11 AF XY: 0.224 AC XY: 101724 AN XY: 454936

African (AFR) AF: 0.476 AC: 10414 AN: 21882

American (AMR) AF: 0.236 AC: 7900 AN: 33440

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 3334 AN: 20712

East Asian (EAS) AF: 0.440 AC: 14759 AN: 33538

South Asian (SAS) AF: 0.306 AC: 20545 AN: 67112

European-Finnish (FIN) AF: 0.179 AC: 7837 AN: 43748

Middle Eastern (MID) AF: 0.186 AC: 847 AN: 4560

European-Non Finnish (NFE) AF: 0.196 AC: 121329 AN: 619498

Other (OTH) AF: 0.238 AC: 9788 AN: 41094

GnomAD4 genome AF: 0.279 AC: 42389 AN: 152072 Hom.: 7122 Cov.: 32 AF XY: 0.279 AC XY: 20767 AN XY: 74340

African (AFR) AF: 0.460 AC: 19059 AN: 41444

American (AMR) AF: 0.239 AC: 3653 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3470

East Asian (EAS) AF: 0.456 AC: 2354 AN: 5162

South Asian (SAS) AF: 0.323 AC: 1557 AN: 4814

European-Finnish (FIN) AF: 0.177 AC: 1876 AN: 10580

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12577 AN: 68002

Other (OTH) AF: 0.240 AC: 507 AN: 2110

Alfa AF: 0.0987 Hom.: 142

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.13
PhyloP100		-1.2
PromoterAI		-0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;