rs1079109

Variant names:

• chr1-161525250-C-T
• rs1079109
• NM_002155.5:c.592C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002155.5(HSPA6):​c.592C>T​(p.Leu198Phe) variant causes a missense change. The variant allele was found at a frequency of 0.111 in 1,613,694 control chromosomes in the GnomAD database, including 11,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (923 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10513 hom.)
• Consequence: HSPA6 NM_002155.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.09
• Publications: 27 publications found

Genes affected

HSPA6 (HGNC:5239): (heat shock protein family A (Hsp70) member 6) Enables enzyme binding activity; heat shock protein binding activity; and unfolded protein binding activity. Involved in cellular response to heat and protein refolding. Located in centriole and cytosol. Colocalizes with COP9 signalosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000273112 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020103753).
• BP6: Variant 1-161525250-C-T is Benign according to our data. Variant chr1-161525250-C-T is described in ClinVar as [Benign]. Clinvar id is 1234232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA6	NM_002155.5	c.592C>T	p.Leu198Phe	missense_variant	Exon 1 of 1	ENST00000309758.6	NP_002146.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA6	ENST00000309758.6	c.592C>T	p.Leu198Phe	missense_variant	Exon 1 of 1	6	NM_002155.5	ENSP00000310219.4

Frequencies

GnomAD3 genomes AF: 0.0949 AC: 14420 AN: 152008 Hom.: 923 Cov.: 32

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.118 AC: 29640 AN: 250810 AF XY: 0.118

Gnomad AFR exome AF: 0.0365

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.262

Gnomad FIN exome AF: 0.0681

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.112 AC: 164317 AN: 1461568 Hom.: 10513 Cov.: 34 AF XY: 0.112 AC XY: 81762 AN XY: 727066

African (AFR) AF: 0.0379 AC: 1270 AN: 33480

American (AMR) AF: 0.117 AC: 5246 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3844 AN: 26134

East Asian (EAS) AF: 0.241 AC: 9550 AN: 39650

South Asian (SAS) AF: 0.0934 AC: 8053 AN: 86228

European-Finnish (FIN) AF: 0.0684 AC: 3653 AN: 53394

Middle Eastern (MID) AF: 0.107 AC: 618 AN: 5766

European-Non Finnish (NFE) AF: 0.112 AC: 124991 AN: 1111830

Other (OTH) AF: 0.117 AC: 7092 AN: 60388

GnomAD4 genome AF: 0.0947 AC: 14411 AN: 152126 Hom.: 923 Cov.: 32 AF XY: 0.0939 AC XY: 6982 AN XY: 74386

African (AFR) AF: 0.0375 AC: 1558 AN: 41542

American (AMR) AF: 0.102 AC: 1564 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 483 AN: 3468

East Asian (EAS) AF: 0.251 AC: 1290 AN: 5146

South Asian (SAS) AF: 0.0995 AC: 478 AN: 4806

European-Finnish (FIN) AF: 0.0665 AC: 705 AN: 10608

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7875 AN: 67964

Other (OTH) AF: 0.106 AC: 224 AN: 2106

Alfa AF: 0.111 Hom.: 350

Bravo AF: 0.0965

ESP6500AA AF: 0.0397 AC: 175

ESP6500EA AF: 0.115 AC: 990

ExAC AF: 0.116 AC: 14094

Asia WGS AF: 0.165 AC: 572 AN: 3476

EpiCase AF: 0.128

EpiControl AF: 0.125

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 28, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31640787) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		4.1
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.21
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.19
ClinPred		0.024	T
GERP RS		2.3
Varity_R		0.77
gMVP		0.14
Mutation Taster		=92/8	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: rs1079109; hg19: chr1-161495040; COSMIC: COSV59062592; COSMIC: COSV59062592;