14-31293508-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015473.4(HEATR5A):​c.5938G>A​(p.Ala1980Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,546 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A1980P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HEATR5A
NM_015473.4 missense

Scores

5
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HEATR5ANM_015473.4 linkc.5938G>A p.Ala1980Thr missense_variant Exon 36 of 36 ENST00000543095.7 NP_056288.2 Q86XA9F5H619

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HEATR5AENST00000543095.7 linkc.5938G>A p.Ala1980Thr missense_variant Exon 36 of 36 5 NM_015473.4 ENSP00000437968.2 F5H619
HEATR5AENST00000538864.6 linkc.4594G>A p.Ala1532Thr missense_variant Exon 28 of 28 5 ENSP00000439979.2 H7C5W6
HEATR5AENST00000551414.1 linkn.2131G>A non_coding_transcript_exon_variant Exon 3 of 3 2
ENSG00000257831ENST00000551799.1 linkn.401-1924C>T intron_variant Intron 4 of 5 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461546
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727060
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.079
T
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.70
D
MetaSVM
Uncertain
0.27
D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-2.3
N
REVEL
Uncertain
0.51
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0040
D
Vest4
0.80
MutPred
0.52
Loss of stability (P = 0.1772);
MVP
0.45
ClinPred
0.94
D
GERP RS
5.7
gMVP
0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-31762714; API