17-60047343-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022070.5(HEATR6):​c.2735G>A​(p.Arg912Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

HEATR6
NM_022070.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07842353).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HEATR6NM_022070.5 linkc.2735G>A p.Arg912Gln missense_variant Exon 18 of 20 ENST00000184956.11 NP_071353.4 Q6AI08

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HEATR6ENST00000184956.11 linkc.2735G>A p.Arg912Gln missense_variant Exon 18 of 20 1 NM_022070.5 ENSP00000184956.5 Q6AI08
HEATR6ENST00000587003.5 linkn.*1506G>A non_coding_transcript_exon_variant Exon 18 of 20 1 ENSP00000466192.1 K7ELR8
HEATR6ENST00000587003.5 linkn.*1506G>A 3_prime_UTR_variant Exon 18 of 20 1 ENSP00000466192.1 K7ELR8

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152086
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000725
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
250838
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135634
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000685
AC:
10
AN:
1460904
Hom.:
0
Cov.:
29
AF XY:
0.00000550
AC XY:
4
AN XY:
726804
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
Gnomad4 AMR exome
AF:
0.00
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:
0.00000270
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152086
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.0000725
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000354
Hom.:
0
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2735G>A (p.R912Q) alteration is located in exon 18 (coding exon 18) of the HEATR6 gene. This alteration results from a G to A substitution at nucleotide position 2735, causing the arginine (R) at amino acid position 912 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
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
12
DANN
Benign
0.97
DEOGEN2
Benign
0.013
T;T;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.33
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.84
T;T;T
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.078
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.40
N;.;.
PrimateAI
Benign
0.21
T
PROVEAN
Benign
0.70
N;.;.
REVEL
Benign
0.020
Sift
Benign
0.64
T;.;.
Sift4G
Benign
0.56
T;T;T
Polyphen
0.010
B;.;.
Vest4
0.14
MVP
0.66
MPC
0.15
ClinPred
0.095
T
GERP RS
3.2
Varity_R
0.014
gMVP
0.070

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs151133736; hg19: chr17-58124704; API