dbSNP rs776775910: HLTF:p.Ala886Val (chr3-149039188-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003071.4(HLTF):c.2657C>T(p.Ala886Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,453,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A886D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

HLTF
NM_003071.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.98

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2898033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLTF	NM_003071.4 link	c.2657C>T	p.Ala886Val	missense_variant	Exon 23 of 25	ENST00000310053.10	NP_003062.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLTF	ENST00000310053.10 link	c.2657C>T	p.Ala886Val	missense_variant	Exon 23 of 25	1	NM_003071.4	ENSP00000308944.5		Q14527-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000247

AC:

AN:

242780

Hom.:

AF XY:

0.0000457

AC XY:

AN XY:

131384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000209

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1453416

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

722782

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000225

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T;T;T;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

D;.;.;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.29

T;T;T;T;T

MetaSVM

Benign

-0.34

MutationAssessor

Benign

0.77

.;N;N;N;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.076

T;D;D;D;D

Sift4G

Benign

0.066

T;T;T;T;.

Polyphen

0.67

.;P;P;P;.

Vest4

0.42

MutPred

0.42

.;Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);.;

MVP

0.82

MPC

0.48

ClinPred

0.17

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.27

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over