Variant 1-108650278-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001102592.2(HENMT1):c.689G>A(p.Arg230Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,614,094 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0075 ( 25 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 12 hom. )

Consequence

HENMT1
NM_001102592.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.255

Variant links:

Genes affected

HENMT1 (HGNC:26400): (HEN methyltransferase 1) Enables small RNA 2'-O-methyltransferase. Involved in RNA methylation. Predicted to be located in P granule. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

HENMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041174293).

BP6

Variant 1-108650278-C-T is Benign according to our data. Variant chr1-108650278-C-T is described in ClinVar as [Benign]. Clinvar id is 727198.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00751 (1144/152258) while in subpopulation AFR AF= 0.026 (1082/41546). AF 95% confidence interval is 0.0248. There are 25 homozygotes in gnomad4. There are 517 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HENMT1	NM_001102592.2 linkuse as main transcript	c.689G>A	p.Arg230Gln	missense_variant	7/8	ENST00000651461.1
HENMT1	NM_144584.3 linkuse as main transcript	c.689G>A	p.Arg230Gln	missense_variant	7/8
HENMT1	XM_005270411.2 linkuse as main transcript	c.713G>A	p.Arg238Gln	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HENMT1	ENST00000651461.1 linkuse as main transcript	c.689G>A	p.Arg230Gln	missense_variant	7/8		NM_001102592.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00749

AC:

1139

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

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:

0.000132

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00197

AC:

495

AN:

251408

Hom.:

AF XY:

0.00146

AC XY:

199

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0264

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.000837

AC:

1223

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000729

AC XY:

530

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0273

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00751

AC:

1144

AN:

152258

Hom.:

Cov.:

AF XY:

0.00694

AC XY:

517

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0260

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00321

Hom.:

Bravo

AF:

0.00818

ESP6500AA

AF:

0.0241

AC:

106

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00240

AC:

291

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.4

DANN

Benign

0.52

DEOGEN2

Benign

0.0062

T;.;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.46

T;T;.;T

MetaRNN

Benign

0.0041

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.43

N;N;N;N

REVEL

Benign

0.014

Sift

Benign

0.52

T;T;T;T

Sift4G

Benign

0.53

T;T;T;T

Polyphen

0.15

B;.;B;.

Vest4

0.19

MVP

0.055

MPC

0.13

ClinPred

0.0025

GERP RS

-5.3

Varity_R

0.070

gMVP

0.28

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