Variant 14-31293573-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015473.4(HEATR5A):c.5873C>T(p.Ser1958Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

HEATR5A
NM_015473.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.93

Variant links:

Genes affected

HEATR5A (HGNC:20276): (HEAT repeat containing 5A) Predicted to be involved in endocytosis; protein localization; and retrograde transport, endosome to Golgi. Predicted to be located in cytosol. Predicted to be active in endocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

HEATR5A links:

HEATR5A (HGNC:):

HEATR5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.747

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEATR5A	NM_015473.4 linkuse as main transcript	c.5873C>T	p.Ser1958Phe	missense_variant	36/36	ENST00000543095.7	NP_056288.2	Q86XA9F5H619

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HEATR5A	ENST00000543095.7 linkuse as main transcript	c.5873C>T	p.Ser1958Phe	missense_variant	36/36	5	NM_015473.4	ENSP00000437968.2	F5H619
HEATR5A	ENST00000538864.6 linkuse as main transcript	c.4529C>T	p.Ser1510Phe	missense_variant	28/28	5		ENSP00000439979.2	H7C5W6
HEATR5A	ENST00000551414.1 linkuse as main transcript	n.2066C>T		non_coding_transcript_exon_variant	3/3	2
ENSG00000257831	ENST00000551799.1 linkuse as main transcript	n.401-1859G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000117

AC:

AN:

248218

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

134710

show subpopulations

Gnomad AFR exome

AF:

0.000711

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000561

AC:

AN:

1461094

Hom.:

Cov.:

AF XY:

0.0000482

AC XY:

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.000928

Gnomad4 AMR exome

AF:

0.0000897

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000197

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000434

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000129

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.000540

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000993

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2024

The c.5873C>T (p.S1958F) alteration is located in exon 36 (coding exon 35) of the HEATR5A gene. This alteration results from a C to T substitution at nucleotide position 5873, causing the serine (S) at amino acid position 1958 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.75

MetaSVM

Uncertain

0.063

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-4.5

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Vest4

0.91

MVP

0.59

ClinPred

0.54

GERP RS

4.8

gMVP

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over