Variant 14-31302372-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015473.4(HEATR5A):c.5387G>A(p.Arg1796Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000811 in 1,603,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

HEATR5A
NM_015473.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05

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:

ENSG00000257831 (HGNC:):

ENSG00000257831 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3463233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEATR5A	NM_015473.4 linkuse as main transcript	c.5387G>A	p.Arg1796Gln	missense_variant	33/36	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.5387G>A	p.Arg1796Gln	missense_variant	33/36	5	NM_015473.4	ENSP00000437968.2	F5H619
HEATR5A	ENST00000538864.6 linkuse as main transcript	c.4120+2533G>A		intron_variant		5		ENSP00000439979.2	H7C5W6
ENSG00000257831	ENST00000551799.1 linkuse as main transcript	n.608C>T		non_coding_transcript_exon_variant	6/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000860

AC:

AN:

232546

Hom.:

AF XY:

0.00000797

AC XY:

AN XY:

125452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000589

Gnomad SAS exome

AF:

0.0000356

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000758

AC:

AN:

1452002

Hom.:

Cov.:

AF XY:

0.00000832

AC XY:

AN XY:

721118

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000723

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151924

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Apr 19, 2024

The c.5387G>A (p.R1796Q) alteration is located in exon 33 (coding exon 32) of the HEATR5A gene. This alteration results from a G to A substitution at nucleotide position 5387, causing the arginine (R) at amino acid position 1796 to be replaced by a glutamine (Q). 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

0.018

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.021

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

M_CAP

Benign

0.062

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.99

REVEL

Uncertain

0.30

Sift

Benign

0.26

Sift4G

Benign

0.37

Vest4

0.66

MutPred

0.36

Loss of MoRF binding (P = 0.0332);

MVP

0.12

ClinPred

0.17

GERP RS

4.0

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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