Variant 3-149040093-G-A 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.2440C>T(p.Pro814Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00451 in 1,610,248 control chromosomes in the GnomAD database, including 28 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 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 27 hom. )

Consequence

HLTF
NM_003071.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.40

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:

HLTF (HGNC:):

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=0.008943468).

BP6

Variant 3-149040093-G-A is Benign according to our data. Variant chr3-149040093-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041292.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLTF	NM_003071.4 linkuse as main transcript	c.2440C>T	p.Pro814Ser	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.2440C>T	p.Pro814Ser	missense_variant	21/25	1	NM_003071.4	ENSP00000308944.5		Q14527-1

Frequencies

GnomAD3 genomes

AF:

0.00268

AC:

407

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00457

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00338

AC:

843

AN:

249714

Hom.:

AF XY:

0.00344

AC XY:

465

AN XY:

135110

show subpopulations

Gnomad AFR exome

AF:

0.000679

Gnomad AMR exome

AF:

0.00137

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00234

Gnomad NFE exome

AF:

0.00625

Gnomad OTH exome

AF:

0.00378

GnomAD4 exome

AF:

0.00470

AC:

6850

AN:

1458048

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

3280

AN XY:

725528

show subpopulations

Gnomad4 AFR exome

AF:

0.000658

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00323

Gnomad4 NFE exome

AF:

0.00578

Gnomad4 OTH exome

AF:

0.00292

GnomAD4 genome

AF:

0.00267

AC:

407

AN:

152200

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.00457

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00416

Hom.:

Bravo

AF:

0.00252

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00413

AC:

501

Asia WGS

AF:

0.000289

AC:

AN:

3474

EpiCase

AF:

0.00338

EpiControl

AF:

0.00457

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

Dec 23, 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

Benign

0.086

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

.;T;T;T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

D;.;.;D;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.0089

T;T;T;T;T

MetaSVM

Uncertain

-0.034

MutationAssessor

Uncertain

2.1

.;M;M;M;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.28

Sift

Benign

0.041

D;D;D;D;D

Sift4G

Benign

0.22

T;T;T;T;.

Polyphen

0.94

.;P;P;P;.

Vest4

0.20

MVP

0.89

MPC

0.57

ClinPred

0.025

GERP RS

5.5

Varity_R

0.046

gMVP

0.38

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