3-149040062-T-C

Variant names:

• chr3-149040062-T-C
• rs74927267
• NM_003071.4:c.2471A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003071.4(HLTF):​c.2471A>G​(p.Lys824Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,459,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. K824T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: HLTF NM_003071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10365459).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLTF	NM_003071.4	MANE Select	c.2471A>G	p.Lys824Arg	missense	Exon 21 of 25	NP_003062.2
	HLTF	NM_001318935.2		c.2471A>G	p.Lys824Arg	missense	Exon 21 of 26	NP_001305864.1	Q14527-1
	HLTF	NM_139048.3		c.2471A>G	p.Lys824Arg	missense	Exon 21 of 26	NP_620636.1	Q14527-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLTF	ENST00000310053.10	TSL:1 MANE Select	c.2471A>G	p.Lys824Arg	missense	Exon 21 of 25	ENSP00000308944.5	Q14527-1
	HLTF	ENST00000392912.6	TSL:1	c.2471A>G	p.Lys824Arg	missense	Exon 21 of 26	ENSP00000376644.2	Q14527-1
	HLTF	ENST00000465259.5	TSL:1	c.2468A>G	p.Lys823Arg	missense	Exon 21 of 25	ENSP00000420745.1	A0A0C4DGA6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249782 AF XY: 0.00000740

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000329 AC: 48 AN: 1459212 Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 20 AN XY: 726012

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.00 AC: 0 AN: 86012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111028

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.69
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.64	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.9
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.078
Sift	Benign	0.29	T
Sift4G	Benign	0.45	T
Polyphen		0.22	B
Vest4		0.055
MutPred		0.26		Loss of ubiquitination at K824 (P = 0.0023)
MVP		0.90
MPC		0.15
ClinPred		0.057	T
GERP RS		-0.087
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.031
gMVP		0.27
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs74927267; hg19: chr3-148757849;