Genetic Variant NM_006597.6:c.1074A>G (chr11-123059519-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006597.6(HSPA8):c.1074A>G(p.Glu358Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,614,138 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 4 hom. )

Consequence

HSPA8
NM_006597.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.409

Publications

0 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:

SNORD14C (HGNC:30352): (small nucleolar RNA, C/D box 14C)

SNORD14C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 11-123059519-T-C is Benign according to our data. Variant chr11-123059519-T-C is described in ClinVar as Benign. ClinVar VariationId is 786217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.409 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00765 (1165/152276) while in subpopulation AFR AF = 0.0256 (1064/41554). AF 95% confidence interval is 0.0243. There are 15 homozygotes in GnomAd4. There are 544 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1165 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSPA8	NM_006597.6	MANE Select	c.1074A>G	p.Glu358Glu	synonymous	Exon 5 of 9	NP_006588.1	P11142-1
HSPA8	NM_153201.4		c.1074A>G	p.Glu358Glu	synonymous	Exon 5 of 8	NP_694881.1	P11142-2
SNORD14C	NR_001453.2		n.-97A>G		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.1074A>G	p.Glu358Glu	synonymous	Exon 5 of 9	ENSP00000432083.1	P11142-1
HSPA8	ENST00000227378.7	TSL:1	c.1074A>G	p.Glu358Glu	synonymous	Exon 4 of 8	ENSP00000227378.3	P11142-1
HSPA8	ENST00000453788.6	TSL:1	c.1074A>G	p.Glu358Glu	synonymous	Exon 5 of 8	ENSP00000404372.2	P11142-2

Frequencies

GnomAD3 genomes

AF:

0.00762

AC:

1160

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00172

AC:

433

AN:

251444

AF XY:

0.00133

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000717

AC:

1048

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000576

AC XY:

419

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0256

AC:

856

AN:

33474

American (AMR)

AF:

0.00154

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111996

Other (OTH)

AF:

0.00177

AC:

107

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

117

176

234

293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00765

AC:

1165

AN:

152276

Hom.:

Cov.:

AF XY:

0.00731

AC XY:

544

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0256

AC:

1064

AN:

41554

American (AMR)

AF:

0.00517

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68032

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

128

193

257

321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00407

Hom.:

Bravo

AF:

0.00891

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.9

(source)

DANN

Benign

0.86

PhyloP100

0.41

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over