Genetic Variant HEATR3:p.Pro16Leu (chr16-50066178-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_182922.4(HEATR3):c.47C>T(p.Pro16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,442,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HEATR3
NM_182922.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32

Publications

1 publications found

Variant links:

Genes affected

HEATR3 (HGNC:26087): (HEAT repeat containing 3) The protein encoded by this gene plays a role in ribosomal protein transport and in the assembly of the 5S ribonucleoprotein particle (5S RNP). The encoded protein also may be involved in NOD2-mediated NF-kappaB signaling. [provided by RefSeq, Jul 2016]

HEATR3 links:

HEATR3-AS1 (HGNC:55406): (HEATR3 antisense RNA 1)

HEATR3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39406633).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182922.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEATR3	NM_182922.4	MANE Select	c.47C>T	p.Pro16Leu	missense	Exon 1 of 15	NP_891552.1	Q7Z4Q2-1
HEATR3	NM_001329729.2		c.-646C>T		5_prime_UTR	Exon 1 of 16	NP_001316658.1
HEATR3	NM_001329730.2		c.-620C>T		5_prime_UTR	Exon 1 of 16	NP_001316659.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEATR3	ENST00000299192.8	TSL:1 MANE Select	c.47C>T	p.Pro16Leu	missense	Exon 1 of 15	ENSP00000299192.7	Q7Z4Q2-1
HEATR3	ENST00000887924.1		c.47C>T	p.Pro16Leu	missense	Exon 1 of 15	ENSP00000557983.1
HEATR3	ENST00000887923.1		c.47C>T	p.Pro16Leu	missense	Exon 1 of 14	ENSP00000557982.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000471

AC:

AN:

212172

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000832

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000139

AC:

AN:

1442284

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715854

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32634

American (AMR)

AF:

0.00

AC:

AN:

41872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25470

East Asian (EAS)

AF:

0.00

AC:

AN:

38812

South Asian (SAS)

AF:

0.00

AC:

AN:

83234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50832

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1104036

Other (OTH)

AF:

0.00

AC:

AN:

59690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

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

Benign

0.28

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Benign

-0.047

Eigen_PC

Benign

0.028

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.88

MutationAssessor

Benign

2.0

PhyloP100

2.3

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.4

REVEL

Benign

0.16

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

0.80

Vest4

0.40

MutPred

0.26

Gain of MoRF binding (P = 0.0584)

MVP

0.71

MPC

0.79

ClinPred

0.97

GERP RS

4.4

PromoterAI

0.077

Neutral

(source)

Varity_R

0.46

gMVP

0.50

Mutation Taster

=77/23

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over