1-91262505-AG-A

Variant names:

• chr1-91262505-AG-A
• rs1557742504
• NM_001017975.6:c.4061delC

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001017975.6(HFM1):​c.4061delC​(p.Pro1354LeufsTer71) variant causes a frameshift 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 (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HFM1 NM_001017975.6 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.58

Genes affected

HFM1 (HGNC:20193): (helicase for meiosis 1) The protein encoded by this gene is thought to be an ATP-dependent DNA helicase and is expressed mainly in germ-line cells. Defects in this gene are a cause of premature ovarian failure 9 (POF9). [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HFM1	NM_001017975.6	c.4061delC	p.Pro1354LeufsTer71	frameshift_variant	Exon 37 of 39	ENST00000370425.8	NP_001017975.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HFM1	ENST00000370425.8	c.4061delC	p.Pro1354LeufsTer71	frameshift_variant	Exon 37 of 39	1	NM_001017975.6	ENSP00000359454.3
HFM1	ENST00000430465.1	c.1694delC	p.Pro565fs	frameshift_variant	Exon 18 of 19	1		ENSP00000387661.1
HFM1	ENST00000462405.5	n.1896delC		non_coding_transcript_exon_variant	Exon 19 of 21	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Premature ovarian failure 9 Uncertain:1

-

Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs1557742504; hg19: chr1-91728062;