3-149032367-A-C

Variant names:

• chr3-149032367-A-C
• NM_003071.4:c.2883T>G

Variant summary

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

The NM_003071.4(HLTF):​c.2883T>G​(p.Ile961Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HLTF NM_003071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLTF	NM_003071.4	c.2883T>G	p.Ile961Met	missense_variant	Exon 25 of 25	ENST00000310053.10	NP_003062.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLTF	ENST00000310053.10	c.2883T>G	p.Ile961Met	missense_variant	Exon 25 of 25	1	NM_003071.4	ENSP00000308944.5
HLTF	ENST00000392912.6	c.2883T>G	p.Ile961Met	missense_variant	Exon 25 of 26	1		ENSP00000376644.2
HLTF	ENST00000465259.5	c.2880T>G	p.Ile960Met	missense_variant	Exon 25 of 25	1		ENSP00000420745.1
HLTF	ENST00000494055.5	c.2883T>G	p.Ile961Met	missense_variant	Exon 25 of 26	2		ENSP00000420429.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2883T>G (p.I961M) alteration is located in exon 25 (coding exon 25) of the HLTF gene. This alteration results from a T to G substitution at nucleotide position 2883, causing the isoleucine (I) at amino acid position 961 to be replaced by a methionine (M). 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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	.;T;T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.96	D;.;.;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.8	.;L;L;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.97	.;D;D;D
Vest4		0.67
MutPred		0.63		.;Gain of disorder (P = 0.0495);Gain of disorder (P = 0.0495);Gain of disorder (P = 0.0495);
MVP		0.50
MPC		0.71
ClinPred		0.87	D
GERP RS		4.6
Varity_R		0.22
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-148750154;