rs199858483

Variant names:

• chr5-138558545-TA-T
• rs199858483
• NM_004134.7:c.1515+7delT

Your query was ambiguous. Multiple possible variants found:

• chr5-138558545-TA-T
• chr5-138558545-TA-TAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004134.7(HSPA9):​c.1515+7delT 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:2
• Conservation: PhyloP100: 3.49
• Publications: 0 publications found

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]

HSPA9 Gene-Disease associations (from GenCC):

• autosomal dominant sideroblastic anemia

  Inheritance: AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• even-plus syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• autosomal recessive sideroblastic anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000299264 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 786063.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004134.7. 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
	HSPA9	NM_004134.7	MANE Select	c.1515+7delT		splice_region intron	N/A	NP_004125.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA9	ENST00000297185.9	TSL:1 MANE Select	c.1515+7delT		splice_region intron	N/A	ENSP00000297185.3	P38646
	HSPA9	ENST00000946847.1		c.1698+7delT		splice_region intron	N/A	ENSP00000616906.1
	HSPA9	ENST00000936338.1		c.1533+7delT		splice_region intron	N/A	ENSP00000606397.1

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

GnomAD2 exomes AF: 0.00196 AC: 492 AN: 251366 AF XY: 0.00131

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 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

African (AFR) AF: 0.0254 AC: 810 AN: 31922

American (AMR) AF: 0.00186 AC: 83 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.000623 AC: 16 AN: 25674

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39328

South Asian (SAS) AF: 0.0000709 AC: 6 AN: 84686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00340 AC: 19 AN: 5596

European-Non Finnish (NFE) AF: 0.0000548 AC: 57 AN: 1040372

Other (OTH) AF: 0.00182 AC: 105 AN: 57712

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

African (AFR) AF: 0.0253 AC: 1051 AN: 41542

American (AMR) AF: 0.00490 AC: 75 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68024

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	HSPA9-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5
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: rs199858483; hg19: chr5-137894234;