5-138558545-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004134.7(HSPA9):c.1515+7del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,535,588 control chromosomes in the GnomAD database, including 32 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (18 hom.)
• Consequence: HSPA9 NM_004134.7 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.49

Genes affected

HSPA9 (HGNC:5244): (heat shock protein family A (Hsp70) member 9) This gene encodes a member of the heat shock protein 70 gene family. The encoded protein is primarily localized to the mitochondria but is also found in the endoplasmic reticulum, plasma membrane and cytoplasmic vesicles. This protein is a heat-shock cognate protein. This protein plays a role in cell proliferation, stress response and maintenance of the mitochondria. A pseudogene of this gene is found on chromosome 2.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-138558545-TA-T is Benign according to our data. Variant chr5-138558545-TA-T is described in ClinVar as [Benign]. Clinvar id is 786063.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-138558545-TA-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00757 (1153/152282) while in subpopulation AFR AF= 0.0253 (1051/41542). AF 95% confidence interval is 0.024. There are 14 homozygotes in gnomad4. There are 544 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1135 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA9	NM_004134.7	c.1515+7del		splice_region_variant, intron_variant		ENST00000297185.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA9	ENST00000297185.9	c.1515+7del		splice_region_variant, intron_variant		1	NM_004134.7	P1

Frequencies

GnomAD3 genomes AF: 0.00746 AC: 1135 AN: 152164 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00196 AC: 492 AN: 251366 Hom.: 7 AF XY: 0.00131 AC XY: 178 AN XY: 135860

Gnomad AFR exome AF: 0.0261

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000793 AC: 1097 AN: 1383306 Hom.: 18 Cov.: 23 AF XY: 0.000668 AC XY: 463 AN XY: 693032

Gnomad4 AFR exome AF: 0.0254

Gnomad4 AMR exome AF: 0.00186

Gnomad4 ASJ exome AF: 0.000623

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.0000709

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000548

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.00757 AC: 1153 AN: 152282 Hom.: 14 Cov.: 32 AF XY: 0.00730 AC XY: 544 AN XY: 74470

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00434 Hom.: 1

Bravo AF: 0.00893

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs199858483; hg19: chr5-137894234;