11-123057914-A-T

Variant names:

• chr11-123057914-A-T
• rs4802
• NM_006597.6:c.1761T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006597.6(HSPA8):​c.1761T>A​(p.Ala587Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSPA8 NM_006597.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• 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]

SNORD14E (HGNC:30354): (small nucleolar RNA, C/D box 14E)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-1.44 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA8	NM_006597.6	c.1761T>A	p.Ala587Ala	synonymous_variant	Exon 9 of 9	ENST00000534624.6	NP_006588.1
HSPA8	XM_011542798.2	c.1761T>A	p.Ala587Ala	synonymous_variant	Exon 9 of 9		XP_011541100.1
HSPA8	NM_153201.4	c.1388-86T>A		intron_variant	Intron 7 of 7		NP_694881.1
SNORD14E	NR_003125.2	n.*163T>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000534624.6	c.1761T>A	p.Ala587Ala	synonymous_variant	Exon 9 of 9	1	NM_006597.6	ENSP00000432083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.88e-7 AC: 1 AN: 1453152 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722672

African (AFR) AF: 0.00 AC: 0 AN: 33064

American (AMR) AF: 0.00 AC: 0 AN: 42652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25676

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 84818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108268

Other (OTH) AF: 0.00 AC: 0 AN: 60020

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4802; hg19: chr11-122928622;