5-138567395-A-G

Variant names:

• chr5-138567395-A-G
• rs256014
• NM_004134.7:c.716+60T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004134.7(HSPA9):​c.716+60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,348,552 control chromosomes in the GnomAD database, including 144,853 homozygotes. 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: 𝑓 0.52 (23084 hom., cov: 32)
  • Exomes 𝑓: 0.44 (121769 hom.)
• Consequence: HSPA9 NM_004134.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 7 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: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA9	NM_004134.7	MANE Select	c.716+60T>C		intron	N/A	NP_004125.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA9	ENST00000297185.9	TSL:1 MANE Select	c.716+60T>C		intron	N/A	ENSP00000297185.3
	HSPA9	ENST00000507115.6	TSL:3	c.716+60T>C		intron	N/A	ENSP00000423759.2
	HSPA9	ENST00000677425.1		c.716+60T>C		intron	N/A	ENSP00000503066.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79481 AN: 151940 Hom.: 23034 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.437 AC: 522389 AN: 1196494 Hom.: 121769 Cov.: 17 AF XY: 0.443 AC XY: 269672 AN XY: 608132

African (AFR) AF: 0.753 AC: 21292 AN: 28264

American (AMR) AF: 0.393 AC: 17253 AN: 43886

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 10527 AN: 24458

East Asian (EAS) AF: 0.812 AC: 31192 AN: 38396

South Asian (SAS) AF: 0.638 AC: 51239 AN: 80310

European-Finnish (FIN) AF: 0.374 AC: 19886 AN: 53148

Middle Eastern (MID) AF: 0.546 AC: 2270 AN: 4160

European-Non Finnish (NFE) AF: 0.395 AC: 345006 AN: 872460

Other (OTH) AF: 0.461 AC: 23724 AN: 51412

GnomAD4 genome AF: 0.523 AC: 79587 AN: 152058 Hom.: 23084 Cov.: 32 AF XY: 0.526 AC XY: 39102 AN XY: 74326

African (AFR) AF: 0.755 AC: 31323 AN: 41460

American (AMR) AF: 0.429 AC: 6552 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1500 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4163 AN: 5168

South Asian (SAS) AF: 0.647 AC: 3122 AN: 4822

European-Finnish (FIN) AF: 0.376 AC: 3968 AN: 10566

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27242 AN: 67968

Other (OTH) AF: 0.502 AC: 1061 AN: 2114

Alfa AF: 0.468 Hom.: 2381

Bravo AF: 0.536

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.89
DANN	Benign	0.65
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs256014; hg19: chr5-137903084;