Genetic Variant HEATR6:p.Ser926Asn (chr17-60046222-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022070.5(HEATR6):c.2777G>A(p.Ser926Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,592,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

HEATR6
NM_022070.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022070.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR6	NM_022070.5	MANE Select	c.2777G>A	p.Ser926Asn	missense	Exon 19 of 20	NP_071353.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEATR6	ENST00000184956.11	TSL:1 MANE Select	c.2777G>A	p.Ser926Asn	missense	Exon 19 of 20	ENSP00000184956.5	Q6AI08
HEATR6	ENST00000587003.5	TSL:1	n.*1548G>A		non_coding_transcript_exon	Exon 19 of 20	ENSP00000466192.1	K7ELR8
HEATR6	ENST00000587003.5	TSL:1	n.*1548G>A		3_prime_UTR	Exon 19 of 20	ENSP00000466192.1	K7ELR8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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

GnomAD2 exomes

AF:

0.0000340

AC:

AN:

235550

AF XY:

0.0000234

show subpopulations

Gnomad AFR exome

AF:

0.0000643

Gnomad AMR exome

AF:

0.0000334

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000286

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000625

AC:

AN:

1440410

Hom.:

Cov.:

AF XY:

0.00000559

AC XY:

AN XY:

715572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32088

American (AMR)

AF:

0.0000252

AC:

AN:

39638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25096

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39492

South Asian (SAS)

AF:

0.00

AC:

AN:

83168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.00000544

AC:

AN:

1103020

Other (OTH)

AF:

0.00

AC:

AN:

59338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74444

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41532

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2114

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000000888178), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-0.39

MutationAssessor

Pathogenic

2.9

PhyloP100

4.9

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.3

REVEL

Benign

0.29

Sift

Benign

0.20

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.85

MVP

0.84

MPC

0.52

ClinPred

0.82

GERP RS

5.4

Varity_R

0.48

gMVP

0.55

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over