rs17268499

Variant names:

• chr10-14866572-C-T
• rs17268499
• NM_016299.4:c.994-511C>T

Variant summary

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

The NM_016299.4(HSPA14):​c.994-511C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,040 control chromosomes in the GnomAD database, including 1,219 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 0.12 (1219 hom., cov: 32)
• Consequence: HSPA14 NM_016299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 2 publications found

Genes affected

HSPA14 (HGNC:29526): (heat shock protein family A (Hsp70) member 14) Predicted to enable several functions, including ATP binding activity; misfolded protein binding activity; and unfolded protein binding activity. Predicted to be involved in several processes, including cellular response to unfolded protein; chaperone cofactor-dependent protein refolding; and protein refolding. Located in cytosol. Colocalizes with ribosome. [provided by Alliance of Genome Resources, Apr 2022]

SUV39H2-DT (HGNC:55188): (SUV39H2 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA14	NM_016299.4	c.994-511C>T		intron_variant	Intron 10 of 13	ENST00000378372.8	NP_057383.2
SUV39H2-DT	NR_199704.1	n.487G>A		non_coding_transcript_exon_variant	Exon 3 of 3
SUV39H2-DT	NR_199703.1	n.393-183G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA14	ENST00000378372.8	c.994-511C>T		intron_variant	Intron 10 of 13	1	NM_016299.4	ENSP00000367623.3
SUV39H2-DT	ENST00000731019.1	n.401+1145G>A		intron_variant	Intron 2 of 2
SUV39H2-DT	ENST00000731020.1	n.435+1145G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18123 AN: 151922 Hom.: 1219 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.00557

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18131 AN: 152040 Hom.: 1219 Cov.: 32 AF XY: 0.119 AC XY: 8847 AN XY: 74310

African (AFR) AF: 0.0730 AC: 3030 AN: 41490

American (AMR) AF: 0.114 AC: 1738 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 343 AN: 3472

East Asian (EAS) AF: 0.00578 AC: 30 AN: 5190

South Asian (SAS) AF: 0.108 AC: 519 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1587 AN: 10530

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10481 AN: 67956

Other (OTH) AF: 0.116 AC: 244 AN: 2112

Alfa AF: 0.144 Hom.: 766

Bravo AF: 0.113

Asia WGS AF: 0.0620 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.33
PhyloP100		0.28
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: rs17268499; hg19: chr10-14908571;