5-138567395-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004134.7(HSPA9):​c.716+60T>A variant causes a intron 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA9	NM_004134.7	c.716+60T>A		intron_variant	Intron 7 of 16	ENST00000297185.9	NP_004125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA9	ENST00000297185.9	c.716+60T>A		intron_variant	Intron 7 of 16	1	NM_004134.7	ENSP00000297185.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1198862 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 609200

African (AFR) AF: 0.00 AC: 0 AN: 28292

American (AMR) AF: 0.00 AC: 0 AN: 43896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24476

East Asian (EAS) AF: 0.00 AC: 0 AN: 38400

South Asian (SAS) AF: 0.00 AC: 0 AN: 80358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4168

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 874620

Other (OTH) AF: 0.00 AC: 0 AN: 51488

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	0.72
DANN	Benign	0.64
PhyloP100		-0.26

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;