10-14867207-T-C

Variant names:

• chr10-14867207-T-C
• rs762612115
• NM_016299.4:c.1118T>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.1118T>C​(p.Ile373Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,286 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HSPA14 NM_016299.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.931
• 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]

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

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=0.20144442).

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.1118T>C	p.Ile373Thr	missense	Exon 11 of 14	NP_057383.2	Q0VDF9
	SUV39H2-DT	NR_186427.1		n.424A>G		non_coding_transcript_exon	Exon 3 of 3
	SUV39H2-DT	NR_186428.1		n.902A>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA14	ENST00000378372.8	TSL:1 MANE Select	c.1118T>C	p.Ile373Thr	missense	Exon 11 of 14	ENSP00000367623.3	Q0VDF9
	SUV39H2-DT	ENST00000731021.1		n.314A>G		non_coding_transcript_exon	Exon 3 of 3
	SUV39H2-DT	ENST00000731022.1		n.485A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251270 AF XY: 0.00

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: 0.00000137 AC: 2 AN: 1461286 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726992

African (AFR) AF: 0.0000299 AC: 1 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111572

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.93
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.15
Sift	Uncertain	0.025	D
Sift4G	Benign	0.18	T
Polyphen		0.0020	B
Vest4		0.29
MutPred		0.70		Loss of helix (P = 0.079)
MVP		0.21
MPC		0.38
ClinPred		0.25	T
GERP RS		0.67
Varity_R		0.080
gMVP		0.59
Mutation Taster		=83/17	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: rs762612115; hg19: chr10-14909206;