Variant chr3-149040122-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003071.4(HLTF):c.2411T>C(p.Ile804Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,609,312 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 11 hom. )

Consequence

HLTF
NM_003071.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.56

Variant links:

Genes affected

HLTF (HGNC:11099): (helicase like transcription factor) This gene encodes a member of the SWI/SNF family. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein contains a RING finger DNA binding motif. Two transcript variants encoding the same protein have been found for this gene. However, use of an alternative translation start site produces an isoform that is truncated at the N-terminus compared to the full-length protein. [provided by RefSeq, Jul 2008]

HLTF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009617865).

BP6

Variant 3-149040122-A-G is Benign according to our data. Variant chr3-149040122-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3056755.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLTF	NM_003071.4 linkuse as main transcript	c.2411T>C	p.Ile804Thr	missense_variant	21/25	ENST00000310053.10	NP_003062.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLTF	ENST00000310053.10 linkuse as main transcript	c.2411T>C	p.Ile804Thr	missense_variant	21/25	1	NM_003071.4	ENSP00000308944	P4	Q14527-1

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

410

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00407

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00273

AC:

679

AN:

248546

Hom.:

AF XY:

0.00266

AC XY:

358

AN XY:

134522

show subpopulations

Gnomad AFR exome

AF:

0.000556

Gnomad AMR exome

AF:

0.00230

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000463

Gnomad FIN exome

AF:

0.000928

Gnomad NFE exome

AF:

0.00448

Gnomad OTH exome

AF:

0.00396

GnomAD4 exome

AF:

0.00339

AC:

4938

AN:

1457030

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

2427

AN XY:

724964

show subpopulations

Gnomad4 AFR exome

AF:

0.000659

Gnomad4 AMR exome

AF:

0.00247

Gnomad4 ASJ exome

AF:

0.00265

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000711

Gnomad4 FIN exome

AF:

0.00139

Gnomad4 NFE exome

AF:

0.00399

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00269

AC:

410

AN:

152282

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

194

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00407

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00382

Hom.:

Bravo

AF:

0.00264

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00278

AC:

337

Asia WGS

AF:

0.000578

AC:

AN:

3472

EpiCase

AF:

0.00377

EpiControl

AF:

0.00381

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HLTF-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

.;T;T;T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

T;.;.;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.0096

T;T;T;T;T

MetaSVM

Uncertain

0.060

MutationAssessor

Pathogenic

2.9

.;M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.1

D;D;D;D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0060

D;D;D;D;D

Sift4G

Uncertain

0.022

D;D;D;D;.

Polyphen

0.73

.;P;P;P;.

Vest4

0.42

MVP

0.90

MPC

0.29

ClinPred

0.045

GERP RS

5.5

Varity_R

0.25

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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