11-123058699-T-G

Variant names:

• chr11-123058699-T-G
• rs1064585
• NM_006597.6:c.1455A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006597.6(HSPA8):​c.1455A>C​(p.Ile485Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,612,996 control chromosomes in the GnomAD database, including 29,050 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 0.23 (4957 hom., cov: 32)
  • Exomes 𝑓: 0.17 (24093 hom.)
• Consequence: HSPA8 NM_006597.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582
• Publications: 19 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]

SNORD14D (HGNC:30353): (small nucleolar RNA, C/D box 14D)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.582 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	NM_006597.6	MANE Select	c.1455A>C	p.Ile485Ile	synonymous	Exon 7 of 9	NP_006588.1
	HSPA8	NM_153201.4		c.1387+68A>C		intron	N/A	NP_694881.1
	SNORD14D	NR_001454.2		n.*210A>C		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.1455A>C	p.Ile485Ile	synonymous	Exon 7 of 9	ENSP00000432083.1
	HSPA8	ENST00000227378.7	TSL:1	c.1455A>C	p.Ile485Ile	synonymous	Exon 6 of 8	ENSP00000227378.3
	HSPA8	ENST00000524552.5	TSL:1	c.228A>C	p.Ile76Ile	synonymous	Exon 2 of 4	ENSP00000435908.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35140 AN: 151964 Hom.: 4940 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0874

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.185 AC: 46499 AN: 251378 AF XY: 0.184

Gnomad AFR exome AF: 0.404

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.0900

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.174 AC: 254735 AN: 1460914 Hom.: 24093 Cov.: 34 AF XY: 0.176 AC XY: 128161 AN XY: 726838

African (AFR) AF: 0.412 AC: 13763 AN: 33438

American (AMR) AF: 0.178 AC: 7978 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3609 AN: 26128

East Asian (EAS) AF: 0.0909 AC: 3607 AN: 39696

South Asian (SAS) AF: 0.253 AC: 21816 AN: 86236

European-Finnish (FIN) AF: 0.151 AC: 8077 AN: 53334

Middle Eastern (MID) AF: 0.173 AC: 990 AN: 5726

European-Non Finnish (NFE) AF: 0.165 AC: 183804 AN: 1111268

Other (OTH) AF: 0.184 AC: 11091 AN: 60364

GnomAD4 genome AF: 0.231 AC: 35206 AN: 152082 Hom.: 4957 Cov.: 32 AF XY: 0.230 AC XY: 17103 AN XY: 74354

African (AFR) AF: 0.394 AC: 16356 AN: 41464

American (AMR) AF: 0.196 AC: 2993 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3468

East Asian (EAS) AF: 0.0878 AC: 455 AN: 5180

South Asian (SAS) AF: 0.270 AC: 1300 AN: 4816

European-Finnish (FIN) AF: 0.153 AC: 1626 AN: 10594

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11304 AN: 67984

Other (OTH) AF: 0.205 AC: 432 AN: 2106

Alfa AF: 0.197 Hom.: 1572

Bravo AF: 0.241

Asia WGS AF: 0.195 AC: 675 AN: 3478

EpiCase AF: 0.169

EpiControl AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		0.58
PromoterAI		0.060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs1064585; hg19: chr11-122929407; COSMIC: COSV57083583; COSMIC: COSV57083583;