NM_003071.4:c.2603A>T

Variant names:

• chr3-149039593-T-A
• NM_003071.4:c.2603A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003071.4(HLTF):​c.2603A>T​(p.Glu868Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HLTF NM_003071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.30
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.826

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.2603A>T	p.Glu868Val	missense	Exon 22 of 25	NP_003062.2
	HLTF	NM_001318935.2		c.2603A>T	p.Glu868Val	missense	Exon 22 of 26	NP_001305864.1	Q14527-1
	HLTF	NM_139048.3		c.2603A>T	p.Glu868Val	missense	Exon 22 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.2603A>T	p.Glu868Val	missense	Exon 22 of 25	ENSP00000308944.5	Q14527-1
	HLTF	ENST00000392912.6	TSL:1	c.2603A>T	p.Glu868Val	missense	Exon 22 of 26	ENSP00000376644.2	Q14527-1
	HLTF	ENST00000465259.5	TSL:1	c.2600A>T	p.Glu867Val	missense	Exon 22 of 25	ENSP00000420745.1	A0A0C4DGA6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.61		Gain of methylation at K872 (P = 0.0825)
MVP		0.91
MPC		0.52
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.51
gMVP		0.68
Mutation Taster		=35/65	disease causing

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

Other links and lift over

hg19: chr3-148757380;