dbSNP rs747207862: HLTF:p.Arg926Pro (chr3-149039068-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003071.4(HLTF):c.2777G>C(p.Arg926Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,429,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R926Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

HLTF
NM_003071.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

Publications

0 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: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.919

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.2777G>C	p.Arg926Pro	missense	Exon 23 of 25	NP_003062.2
HLTF	NM_001318935.2		c.2777G>C	p.Arg926Pro	missense	Exon 23 of 26	NP_001305864.1	Q14527-1
HLTF	NM_139048.3		c.2777G>C	p.Arg926Pro	missense	Exon 23 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.2777G>C	p.Arg926Pro	missense	Exon 23 of 25	ENSP00000308944.5	Q14527-1
HLTF	ENST00000392912.6	TSL:1	c.2777G>C	p.Arg926Pro	missense	Exon 23 of 26	ENSP00000376644.2	Q14527-1
HLTF	ENST00000465259.5	TSL:1	c.2774G>C	p.Arg925Pro	missense	Exon 23 of 25	ENSP00000420745.1	A0A0C4DGA6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1429560

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31562

American (AMR)

AF:

0.00

AC:

AN:

38112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24800

East Asian (EAS)

AF:

0.00

AC:

AN:

38714

South Asian (SAS)

AF:

0.00

AC:

AN:

80028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52800

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1099120

Other (OTH)

AF:

0.00

AC:

AN:

58814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.45

MutationAssessor

Pathogenic

3.5

PhyloP100

1.4

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-4.0

REVEL

Pathogenic

0.66

Sift

Uncertain

0.010

Sift4G

Uncertain

0.024

Polyphen

1.0

Vest4

0.87

MutPred

0.83

Gain of sheet (P = 0.1451)

MVP

0.90

MPC

0.88

ClinPred

0.99

GERP RS

6.0

Varity_R

0.75

gMVP

0.91

Mutation Taster

=60/40

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over