rs200308045

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_022070.5(HEATR6):​c.2777G>T​(p.Ser926Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. S926N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

HEATR6
NM_022070.5 missense

Scores

7
8
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.92
Variant links:
Genes affected
HEATR6 (HGNC:24076): (HEAT repeat containing 6) Enables RNA binding activity. [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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.86

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HEATR6NM_022070.5 linkc.2777G>T p.Ser926Ile missense_variant Exon 19 of 20 ENST00000184956.11 NP_071353.4 Q6AI08

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HEATR6ENST00000184956.11 linkc.2777G>T p.Ser926Ile missense_variant Exon 19 of 20 1 NM_022070.5 ENSP00000184956.5 Q6AI08
HEATR6ENST00000587003.5 linkn.*1548G>T non_coding_transcript_exon_variant Exon 19 of 20 1 ENSP00000466192.1 K7ELR8
HEATR6ENST00000587003.5 linkn.*1548G>T 3_prime_UTR_variant Exon 19 of 20 1 ENSP00000466192.1 K7ELR8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.59
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.20
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;T;T
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.046
D
MetaRNN
Pathogenic
0.86
D;D;D
MetaSVM
Uncertain
-0.19
T
MutationAssessor
Pathogenic
2.9
M;.;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Uncertain
-2.6
D;.;.
REVEL
Uncertain
0.47
Sift
Benign
0.24
T;.;.
Sift4G
Uncertain
0.0040
D;D;D
Polyphen
1.0
D;.;.
Vest4
0.91
MutPred
0.57
Loss of helix (P = 0.0093);.;.;
MVP
0.82
MPC
0.55
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.55
gMVP
0.59

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: rs200308045; hg19: chr17-58123583; API