Variant chr3-149032267-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003071.4(HLTF):c.2983A>T(p.Met995Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,448,298 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HLTF
NM_003071.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.964

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06927705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLTF	NM_003071.4 linkuse as main transcript	c.2983A>T	p.Met995Leu	missense_variant	25/25	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.2983A>T	p.Met995Leu	missense_variant	25/25	1	NM_003071.4	ENSP00000308944	P4	Q14527-1
HLTF	ENST00000392912.6 linkuse as main transcript	c.2983A>T	p.Met995Leu	missense_variant	25/26	1		ENSP00000376644	P4	Q14527-1
HLTF	ENST00000465259.5 linkuse as main transcript	c.2980A>T	p.Met994Leu	missense_variant	25/25	1		ENSP00000420745	A1
HLTF	ENST00000494055.5 linkuse as main transcript	c.2983A>T	p.Met995Leu	missense_variant	25/26	2		ENSP00000420429	P4	Q14527-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000839

AC:

AN:

238364

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

128872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000634

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1448298

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000479

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.2983A>T (p.M995L) alteration is located in exon 25 (coding exon 25) of the HLTF gene. This alteration results from a A to T substitution at nucleotide position 2983, causing the methionine (M) at amino acid position 995 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.014

.;T;T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.71

T;.;.;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.069

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.33

.;N;N;N

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.51

N;N;N;N

REVEL

Benign

0.066

Sift

Benign

0.45

T;T;T;T

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.0

.;B;B;B

Vest4

0.33

MutPred

0.37

.;Loss of ubiquitination at K999 (P = 0.0675);Loss of ubiquitination at K999 (P = 0.0675);Loss of ubiquitination at K999 (P = 0.0675);

MVP

0.61

MPC

0.17

ClinPred

0.014

GERP RS

2.2

Varity_R

0.037

gMVP

0.53

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