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GeneBe

10-14867256-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016299.4(HSPA14):c.1167T>C(p.Ser389=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,613,780 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0036 ( 28 hom. )

Consequence

HSPA14
NM_016299.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.169
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-14867256-T-C is Benign according to our data. Variant chr10-14867256-T-C is described in ClinVar as [Benign]. Clinvar id is 781938.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.169 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 540 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HSPA14NM_016299.4 linkuse as main transcriptc.1167T>C p.Ser389= synonymous_variant 11/14 ENST00000378372.8
LOC124902382XR_007062064.1 linkuse as main transcriptn.392+461A>G intron_variant, non_coding_transcript_variant
LOC124902382XR_007062065.1 linkuse as main transcriptn.392+461A>G intron_variant, non_coding_transcript_variant
LOC124902382XR_007062066.1 linkuse as main transcriptn.392+461A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HSPA14ENST00000378372.8 linkuse as main transcriptc.1167T>C p.Ser389= synonymous_variant 11/141 NM_016299.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00355
AC:
540
AN:
152216
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000675
Gnomad AMI
AF:
0.00440
Gnomad AMR
AF:
0.0133
Gnomad ASJ
AF:
0.00720
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00642
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.00328
Gnomad OTH
AF:
0.00860
GnomAD3 exomes
AF:
0.00430
AC:
1081
AN:
251232
Hom.:
10
AF XY:
0.00471
AC XY:
640
AN XY:
135790
show subpopulations
Gnomad AFR exome
AF:
0.000492
Gnomad AMR exome
AF:
0.00674
Gnomad ASJ exome
AF:
0.00556
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00761
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00452
Gnomad OTH exome
AF:
0.00604
GnomAD4 exome
AF:
0.00359
AC:
5246
AN:
1461446
Hom.:
28
Cov.:
30
AF XY:
0.00381
AC XY:
2771
AN XY:
727058
show subpopulations
Gnomad4 AFR exome
AF:
0.000717
Gnomad4 AMR exome
AF:
0.00633
Gnomad4 ASJ exome
AF:
0.00555
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00791
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.00334
Gnomad4 OTH exome
AF:
0.00502
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00355
AC:
541
AN:
152334
Hom.:
1
Cov.:
32
AF XY:
0.00385
AC XY:
287
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.000697
Gnomad4 AMR
AF:
0.0133
Gnomad4 ASJ
AF:
0.00720
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00643
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00328
Gnomad4 OTH
AF:
0.00851
Alfa
AF:
0.00344
Hom.:
0
Bravo
AF:
0.00462
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.00507
EpiControl
AF:
0.00652

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 22, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
Cadd
Benign
6.1
Dann
Benign
0.63

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61751214; hg19: chr10-14909255; API