Genetic Variant HEATR6:p.Gln940Arg (chr17-60046180-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_022070.5(HEATR6):c.2819A>G(p.Gln940Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

HEATR6
NM_022070.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.77

Variant links:

Genes affected

HEATR6 (HGNC:24076): (HEAT repeat containing 6) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

HEATR6 links:

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=0.08154431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEATR6	NM_022070.5 link	c.2819A>G	p.Gln940Arg	missense_variant	Exon 19 of 20	ENST00000184956.11	NP_071353.4	Q6AI08

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HEATR6	ENST00000184956.11 link	c.2819A>G	p.Gln940Arg	missense_variant	Exon 19 of 20	1	NM_022070.5	ENSP00000184956.5	Q6AI08
HEATR6	ENST00000587003.5 link	n.*1590A>G		non_coding_transcript_exon_variant	Exon 19 of 20	1		ENSP00000466192.1	K7ELR8
HEATR6	ENST00000587003.5 link	n.*1590A>G		3_prime_UTR_variant	Exon 19 of 20	1		ENSP00000466192.1	K7ELR8

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000478

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251188

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000869

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461668

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000151

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.0000654

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:

0.000473

Alfa

AF:

0.000264

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 09, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2819A>G (p.Q940R) alteration is located in exon 19 (coding exon 19) of the HEATR6 gene. This alteration results from a A to G substitution at nucleotide position 2819, causing the glutamine (Q) at amino acid position 940 to be replaced by an arginine (R). 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

0.091

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.027

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.43

N;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.1

N;.;.

REVEL

Benign

0.048

Sift

Benign

0.31

T;.;.

Sift4G

Benign

0.38

T;T;T

Polyphen

0.033

B;.;.

Vest4

0.22

MVP

0.39

MPC

0.14

ClinPred

0.060

GERP RS

4.4

Varity_R

0.055

gMVP

0.22

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