chr10-14849802-A-C

Variant names:

• chr10-14849802-A-C
• rs538018528
• NM_016299.4:c.458A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016299.4(HSPA14):​c.458A>C​(p.Asn153Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N153S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HSPA14 NM_016299.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13851747).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016299.4. 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
	HSPA14	NM_016299.4	MANE Select	c.458A>C	p.Asn153Thr	missense	Exon 6 of 14	NP_057383.2	Q0VDF9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA14	ENST00000378372.8	TSL:1 MANE Select	c.458A>C	p.Asn153Thr	missense	Exon 6 of 14	ENSP00000367623.3	Q0VDF9
	HSPA14	ENST00000441647.1	TSL:3	c.*326A>C		downstream_gene	N/A	ENSP00000404691.1	H7C2A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250786 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456856 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725056

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.00 AC: 0 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.00 AC: 0 AN: 86046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107772

Other (OTH) AF: 0.00 AC: 0 AN: 60204

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.41	N
PhyloP100		2.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.099
Sift	Benign	0.032	D
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.59		Gain of phosphorylation at N153 (P = 0.035)
MVP		0.18
MPC		0.31
ClinPred		0.15	T
GERP RS		0.69
Varity_R		0.092
gMVP		0.35
Mutation Taster		=87/13	polymorphism

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: rs538018528; hg19: chr10-14891801;