rs115882568

Variant names:

• chr11-123059588-G-A
• rs115882568
• NM_006597.6:c.1005C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-123059588-G-A
• chr11-123059588-G-C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006597.6(HSPA8):​c.1005C>T​(p.Val335Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000412 in 1,614,092 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (2 hom.)
• Consequence: HSPA8 NM_006597.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.09
• Publications: 0 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]

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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 11-123059588-G-A is Benign according to our data. Variant chr11-123059588-G-A is described in ClinVar as Benign. ClinVar VariationId is 791179.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.
• BS2: High AC in GnomAd4 at 320 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	NM_006597.6	MANE Select	c.1005C>T	p.Val335Val	synonymous	Exon 5 of 9	NP_006588.1	P11142-1
	HSPA8	NM_153201.4		c.1005C>T	p.Val335Val	synonymous	Exon 5 of 8	NP_694881.1	P11142-2
	SNORD14C	NR_001453.2		n.-166C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.1005C>T	p.Val335Val	synonymous	Exon 5 of 9	ENSP00000432083.1	P11142-1
	HSPA8	ENST00000227378.7	TSL:1	c.1005C>T	p.Val335Val	synonymous	Exon 4 of 8	ENSP00000227378.3	P11142-1
	HSPA8	ENST00000453788.6	TSL:1	c.1005C>T	p.Val335Val	synonymous	Exon 5 of 8	ENSP00000404372.2	P11142-2

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 320 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00702

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

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: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000533 AC: 134 AN: 251396 AF XY: 0.000456

Gnomad AFR exome AF: 0.00703

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000236 AC: 345 AN: 1461810 Hom.: 2 Cov.: 34 AF XY: 0.000223 AC XY: 162 AN XY: 727218

African (AFR) AF: 0.00839 AC: 281 AN: 33478

American (AMR) AF: 0.000447 AC: 20 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5752

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111960

Other (OTH) AF: 0.000397 AC: 24 AN: 60392

GnomAD4 genome AF: 0.00210 AC: 320 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.00199 AC XY: 148 AN XY: 74470

African (AFR) AF: 0.00700 AC: 291 AN: 41556

American (AMR) AF: 0.00131 AC: 20 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.000998 Hom.: 0

Bravo AF: 0.00261

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.7
DANN	Benign	0.92
PhyloP100		1.1
PromoterAI		-0.0078	Neutral
Mutation Taster		=100/0	polymorphism

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: rs115882568; hg19: chr11-122930296;