Genetic Variant NM_003071.4:c.2471A>C (chr3-149040062-T-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003071.4(HLTF):c.2471A>C(p.Lys824Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,611,494 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

HLTF
NM_003071.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.93

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005200863).

BP6

Variant 3-149040062-T-G is Benign according to our data. Variant chr3-149040062-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3049166.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003071.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HLTF	NM_003071.4	MANE Select	c.2471A>C	p.Lys824Thr	missense	Exon 21 of 25	NP_003062.2
HLTF	NM_001318935.2		c.2471A>C	p.Lys824Thr	missense	Exon 21 of 26	NP_001305864.1	Q14527-1
HLTF	NM_139048.3		c.2471A>C	p.Lys824Thr	missense	Exon 21 of 26	NP_620636.1	Q14527-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HLTF	ENST00000310053.10	TSL:1 MANE Select	c.2471A>C	p.Lys824Thr	missense	Exon 21 of 25	ENSP00000308944.5	Q14527-1
HLTF	ENST00000392912.6	TSL:1	c.2471A>C	p.Lys824Thr	missense	Exon 21 of 26	ENSP00000376644.2	Q14527-1
HLTF	ENST00000465259.5	TSL:1	c.2468A>C	p.Lys823Thr	missense	Exon 21 of 25	ENSP00000420745.1	A0A0C4DGA6

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

221

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00509

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000340

AC:

AN:

249782

AF XY:

0.000252

show subpopulations

Gnomad AFR exome

AF:

0.00494

Gnomad AMR exome

AF:

0.000117

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:

0.000164

GnomAD4 exome

AF:

0.000129

AC:

188

AN:

1459214

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

726014

show subpopulations

African (AFR)

AF:

0.00505

AC:

169

AN:

33436

American (AMR)

AF:

0.0000896

AC:

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39584

South Asian (SAS)

AF:

0.00

AC:

AN:

86012

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111032

Other (OTH)

AF:

0.000232

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.00144

AC:

220

AN:

152280

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00505

AC:

210

AN:

41576

American (AMR)

AF:

0.000261

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67984

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.000703

Hom.:

Bravo

AF:

0.00175

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

HLTF-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.015

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.65

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.68

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.3

PhyloP100

1.9

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.11

REVEL

Benign

0.17

Sift

Benign

0.39

Sift4G

Benign

0.53

Polyphen

0.22

Vest4

0.22

MVP

0.91

MPC

0.27

ClinPred

0.016

GERP RS

-0.087

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.37

Mutation Taster

=90/10

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over