dbSNP rs141489673: HEATR4:p.Arg973Leu (chr14-73478769-C-A) – 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_001220484.1(HEATR4):c.2918G>T(p.Arg973Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HEATR4
NM_001220484.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.45

Variant links:

Genes affected

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

HEATR4 links:

ENSG00000251393 (HGNC:):

ENSG00000251393 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=0.07126522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEATR4	NM_001220484.1 link	c.2918G>T	p.Arg973Leu	missense_variant	Exon 18 of 18	ENST00000553558.6	NP_001207413.1	Q86WZ0
HEATR4	NM_203309.2 link	c.2918G>T	p.Arg973Leu	missense_variant	Exon 17 of 17		NP_976054.2	Q86WZ0
HEATR4	XM_047431370.1 link	c.2918G>T	p.Arg973Leu	missense_variant	Exon 17 of 17		XP_047287326.1
HEATR4	XM_047431371.1 link	c.1649G>T	p.Arg550Leu	missense_variant	Exon 15 of 15		XP_047287327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEATR4	ENST00000553558.6 link	c.2918G>T	p.Arg973Leu	missense_variant	Exon 18 of 18	2	NM_001220484.1	ENSP00000450444.2		Q86WZ0

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.00

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250044

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135304

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727216

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151940

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

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:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.014

DANN

Benign

0.93

DEOGEN2

Benign

0.0039

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.53

.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.69

N;N

REVEL

Benign

0.024

Sift

Benign

0.17

T;T

Sift4G

Uncertain

0.047

D;D

Polyphen

0.17

B;B

Vest4

0.27

MutPred

0.29

Gain of helix (P = 0.027);Gain of helix (P = 0.027);

MVP

0.040

MPC

0.16

ClinPred

0.063

GERP RS

-4.7

Varity_R

0.051

gMVP

0.061

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over