chr3-149039148-G-T

Position:

• chr3-149039148-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003071.4(HLTF):​c.2697C>A​(p.Asn899Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HLTF NM_003071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

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 (HGNC:):

ACMG classification

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=0.22263002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLTF	NM_003071.4	c.2697C>A	p.Asn899Lys	missense_variant	23/25	ENST00000310053.10	NP_003062.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLTF	ENST00000310053.10	c.2697C>A	p.Asn899Lys	missense_variant	23/25	1	NM_003071.4	ENSP00000308944.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.2697C>A (p.N899K) alteration is located in exon 23 (coding exon 23) of the HLTF gene. This alteration results from a C to A substitution at nucleotide position 2697, causing the asparagine (N) at amino acid position 899 to be replaced by a lysine (K). 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	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.093	.;T;T;T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	T;.;.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	.;L;L;L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.45	T;T;T;T;T
Sift4G	Benign	0.28	T;T;T;T;.
Polyphen		0.0030	.;B;B;B;.
Vest4		0.21
MutPred		0.62		.;Gain of ubiquitination at N899 (P = 0.0203);Gain of ubiquitination at N899 (P = 0.0203);Gain of ubiquitination at N899 (P = 0.0203);.;
MVP		0.70
MPC		0.21
ClinPred		0.21	T
GERP RS		2.8
Varity_R		0.066
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-148756935;