chr3-149042177-T-C

Position:

chr3-149042177-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000310053.10(HLTF):c.2186A>G(p.Asn729Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000449 in 1,613,124 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 5 hom. )

Consequence

HLTF
ENST00000310053.10 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.14

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055761933).

BP6

Variant 3-149042177-T-C is Benign according to our data. Variant chr3-149042177-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2381994.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLTF	NM_003071.4 linkuse as main transcript	c.2186A>G	p.Asn729Ser	missense_variant	19/25	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.2186A>G	p.Asn729Ser	missense_variant	19/25	1	NM_003071.4	ENSP00000308944	P4	Q14527-1

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000649

AC:

163

AN:

251226

Hom.:

AF XY:

0.000655

AC XY:

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.000882

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.000775

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000457

AC:

668

AN:

1460892

Hom.:

Cov.:

AF XY:

0.000460

AC XY:

334

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000905

Gnomad4 FIN exome

AF:

0.00189

Gnomad4 NFE exome

AF:

0.000409

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.000374

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.000230

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000791

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000546

EpiControl

AF:

0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

HLTF-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 08, 2021

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

0.045

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.0084

.;T;T;T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.40

T;.;.;T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.0056

T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-1.9

.;N;N;N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.69

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.80

T;T;T;T;.

Polyphen

0.0

.;B;B;B;.

Vest4

0.099

MVP

0.72

MPC

0.14

ClinPred

0.0057

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.015

gMVP

0.12

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