NM_003071.4:c.2440C>T

Variant names:

• chr3-149040093-G-A
• rs61750364
• NM_003071.4:c.2440C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_003071.4(HLTF):​c.2440C>T​(p.Pro814Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00451 in 1,610,248 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (27 hom.)
• Consequence: HLTF NM_003071.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.40
• Publications: 9 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008943468).
• BP6: Variant 3-149040093-G-A is Benign according to our data. Variant chr3-149040093-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3041292.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 27 AR gene

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.2440C>T	p.Pro814Ser	missense	Exon 21 of 25	NP_003062.2
	HLTF	NM_001318935.2		c.2440C>T	p.Pro814Ser	missense	Exon 21 of 26	NP_001305864.1	Q14527-1
	HLTF	NM_139048.3		c.2440C>T	p.Pro814Ser	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.2440C>T	p.Pro814Ser	missense	Exon 21 of 25	ENSP00000308944.5	Q14527-1
	HLTF	ENST00000392912.6	TSL:1	c.2440C>T	p.Pro814Ser	missense	Exon 21 of 26	ENSP00000376644.2	Q14527-1
	HLTF	ENST00000465259.5	TSL:1	c.2437C>T	p.Pro813Ser	missense	Exon 21 of 25	ENSP00000420745.1	A0A0C4DGA6

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 407 AN: 152082 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00208

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00457

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.00338 AC: 843 AN: 249714 AF XY: 0.00344

Gnomad AFR exome AF: 0.000679

Gnomad AMR exome AF: 0.00137

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00234

Gnomad NFE exome AF: 0.00625

Gnomad OTH exome AF: 0.00378

GnomAD4 exome AF: 0.00470 AC: 6850 AN: 1458048 Hom.: 27 Cov.: 30 AF XY: 0.00452 AC XY: 3280 AN XY: 725528

African (AFR) AF: 0.000658 AC: 22 AN: 33418

American (AMR) AF: 0.00123 AC: 55 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.000163 AC: 14 AN: 85964

European-Finnish (FIN) AF: 0.00323 AC: 169 AN: 52332

Middle Eastern (MID) AF: 0.000524 AC: 3 AN: 5726

European-Non Finnish (NFE) AF: 0.00578 AC: 6411 AN: 1110072

Other (OTH) AF: 0.00292 AC: 176 AN: 60284

GnomAD4 genome AF: 0.00267 AC: 407 AN: 152200 Hom.: 1 Cov.: 32 AF XY: 0.00255 AC XY: 190 AN XY: 74404

African (AFR) AF: 0.00116 AC: 48 AN: 41536

American (AMR) AF: 0.00124 AC: 19 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00208 AC: 22 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00457 AC: 311 AN: 67992

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00399 Hom.: 1

Bravo AF: 0.00252

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00395 AC: 34

ExAC AF: 0.00413 AC: 501

Asia WGS AF: 0.000289 AC: 1 AN: 3474

EpiCase AF: 0.00338

EpiControl AF: 0.00457

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HLTF-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.0089	T
MetaSVM	Uncertain	-0.034	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.28
Sift	Benign	0.041	D
Sift4G	Benign	0.22	T
Polyphen		0.94	P
Vest4		0.20
MVP		0.89
MPC		0.57
ClinPred		0.025	T
GERP RS		5.5
Varity_R		0.046
gMVP		0.38
Mutation Taster		=100/0	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: rs61750364; hg19: chr3-148757880; COSMIC: COSV105189285; COSMIC: COSV105189285;