NM_016299.4:c.993+3987C>G

Variant names:

• chr10-14859930-C-G
• rs9787671
• NM_016299.4:c.993+3987C>G

Variant summary

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

The NM_016299.4(HSPA14):​c.993+3987C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,962 control chromosomes in the GnomAD database, including 3,044 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 0.20 (3044 hom., cov: 32)
• Consequence: HSPA14 NM_016299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA14	NM_016299.4	c.993+3987C>G		intron_variant	Intron 10 of 13	ENST00000378372.8	NP_057383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA14	ENST00000378372.8	c.993+3987C>G		intron_variant	Intron 10 of 13	1	NM_016299.4	ENSP00000367623.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29792 AN: 151846 Hom.: 3040 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.196 AC: 29819 AN: 151962 Hom.: 3044 Cov.: 32 AF XY: 0.198 AC XY: 14688 AN XY: 74272

African (AFR) AF: 0.240 AC: 9939 AN: 41452

American (AMR) AF: 0.172 AC: 2628 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1424 AN: 5180

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4816

European-Finnish (FIN) AF: 0.163 AC: 1713 AN: 10512

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11885 AN: 67956

Other (OTH) AF: 0.177 AC: 372 AN: 2106

Alfa AF: 0.0806 Hom.: 101

Bravo AF: 0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.49
PhyloP100		0.017
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: rs9787671; hg19: chr10-14901929;