Genetic Variant NM_006597.6:c.*267T>C (chr11-123057467-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006597.6(HSPA8):c.*267T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 335,620 control chromosomes in the GnomAD database, including 8,140 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 ( 4911 hom., cov: 32)

Exomes 𝑓: 0.17 ( 3229 hom. )

Consequence

HSPA8
NM_006597.6 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.408

Publications

5 publications found

Variant links:

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]

HSPA8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
HSPA8	NM_006597.6 link	c.*267T>C	downstream_gene_variant	ENST00000534624.6	NP_006588.1
HSPA8	NM_153201.4 link	c.*267T>C	downstream_gene_variant		NP_694881.1
HSPA8	XM_011542798.2 link	c.*267T>C	downstream_gene_variant		XP_011541100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000534624.6 link	c.*267T>C		downstream_gene_variant		1	NM_006597.6	ENSP00000432083.1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34993

AN:

152062

Hom.:

4891

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.0881

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.206

GnomAD4 exome

AF:

0.175

AC:

32086

AN:

183440

Hom.:

3229

Cov.:

AF XY:

0.177

AC XY:

16710

AN XY:

94550

show subpopulations

African (AFR)

AF:

0.395

AC:

2017

AN:

5108

American (AMR)

AF:

0.191

AC:

1039

AN:

5430

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

972

AN:

6650

East Asian (EAS)

AF:

0.0912

AC:

1146

AN:

12560

South Asian (SAS)

AF:

0.245

AC:

2625

AN:

10736

European-Finnish (FIN)

AF:

0.156

AC:

1890

AN:

12148

Middle Eastern (MID)

AF:

0.186

AC:

166

AN:

894

European-Non Finnish (NFE)

AF:

0.169

AC:

19915

AN:

117870

Other (OTH)

AF:

0.192

AC:

2316

AN:

12044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

1236

2472

3708

4944

6180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.230

AC:

35062

AN:

152180

Hom.:

4911

Cov.:

AF XY:

0.229

AC XY:

17027

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.391

AC:

16214

AN:

41500

American (AMR)

AF:

0.196

AC:

2994

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

497

AN:

3472

East Asian (EAS)

AF:

0.0885

AC:

458

AN:

5178

South Asian (SAS)

AF:

0.271

AC:

1308

AN:

4828

European-Finnish (FIN)

AF:

0.153

AC:

1625

AN:

10600

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.166

AC:

11298

AN:

67996

Other (OTH)

AF:

0.203

AC:

427

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1313

2626

3940

5253

6566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.212

Hom.:

682

Bravo

AF:

0.239

Asia WGS

AF:

0.202

AC:

699

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.1

(source)

DANN

Benign

0.30

PhyloP100

0.41

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over