NM_003071.4:c.2549C>T

Variant names:

• chr3-149039647-G-A
• rs201738138
• NM_003071.4:c.2549C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003071.4(HLTF):​c.2549C>T​(p.Pro850Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000311 in 1,606,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: HLTF NM_003071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33746657).

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.2549C>T	p.Pro850Leu	missense	Exon 22 of 25	NP_003062.2
	HLTF	NM_001318935.2		c.2549C>T	p.Pro850Leu	missense	Exon 22 of 26	NP_001305864.1	Q14527-1
	HLTF	NM_139048.3		c.2549C>T	p.Pro850Leu	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.2549C>T	p.Pro850Leu	missense	Exon 22 of 25	ENSP00000308944.5	Q14527-1
	HLTF	ENST00000392912.6	TSL:1	c.2549C>T	p.Pro850Leu	missense	Exon 22 of 26	ENSP00000376644.2	Q14527-1
	HLTF	ENST00000465259.5	TSL:1	c.2546C>T	p.Pro849Leu	missense	Exon 22 of 25	ENSP00000420745.1	A0A0C4DGA6

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151914 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 246808 AF XY: 0.00

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: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1454586 Hom.: 0 Cov.: 29 AF XY: 0.00000415 AC XY: 3 AN XY: 723486

African (AFR) AF: 0.00 AC: 0 AN: 33170

American (AMR) AF: 0.00 AC: 0 AN: 43742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25982

East Asian (EAS) AF: 0.00 AC: 0 AN: 39380

South Asian (SAS) AF: 0.00 AC: 0 AN: 84696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1108596

Other (OTH) AF: 0.00 AC: 0 AN: 60042

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152032 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74300

African (AFR) AF: 0.00 AC: 0 AN: 41502

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

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	Benign	0.18
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.6
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.022	D
Polyphen		0.69	P
Vest4		0.32
MutPred		0.34		Loss of glycosylation at P850 (P = 0.0185)
MVP		0.84
MPC		0.25
ClinPred		0.75	D
GERP RS		5.9
Varity_R		0.26
gMVP		0.38
Mutation Taster		=75/25	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: rs201738138; hg19: chr3-148757434;