21-14372948-T-C

Variant names:

• chr21-14372948-T-C
• rs12479
• NM_006948.5:c.*669A>G

Variant summary

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

The NM_006948.5(HSPA13):​c.*669A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,112 control chromosomes in the GnomAD database, including 43,995 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 0.76 (43994 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: HSPA13 NM_006948.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• Publications: 8 publications found

Genes affected

HSPA13 (HGNC:11375): (heat shock protein family A (Hsp70) member 13) The protein encoded by this gene is a member of the heat shock protein 70 family and is found associated with microsomes. Members of this protein family play a role in the processing of cytosolic and secretory proteins, as well as in the removal of denatured or incorrectly-folded proteins. The encoded protein contains an ATPase domain and has been shown to associate with a ubiquitin-like protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006948.5. 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
	HSPA13	NM_006948.5	MANE Select	c.*669A>G		3_prime_UTR	Exon 5 of 5	NP_008879.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA13	ENST00000285667.4	TSL:1 MANE Select	c.*669A>G		3_prime_UTR	Exon 5 of 5	ENSP00000285667.3	P48723
	HSPA13	ENST00000903931.1		c.*669A>G		3_prime_UTR	Exon 4 of 4	ENSP00000573990.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114982 AN: 151992 Hom.: 43957 Cov.: 33

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.748

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.756 AC: 115068 AN: 152110 Hom.: 43994 Cov.: 33 AF XY: 0.753 AC XY: 55975 AN XY: 74370

African (AFR) AF: 0.836 AC: 34705 AN: 41510

American (AMR) AF: 0.637 AC: 9737 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2752 AN: 3470

East Asian (EAS) AF: 0.619 AC: 3202 AN: 5172

South Asian (SAS) AF: 0.685 AC: 3303 AN: 4822

European-Finnish (FIN) AF: 0.733 AC: 7751 AN: 10578

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51091 AN: 67956

Other (OTH) AF: 0.748 AC: 1583 AN: 2116

Alfa AF: 0.748 Hom.: 152004

Bravo AF: 0.749

Asia WGS AF: 0.660 AC: 2294 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.81
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs12479; hg19: chr21-15745269;