rs587777270

Positions:

• chr1-91266060-GGG-GC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001017975.6(HFM1):​c.3929_3930delCCinsG​(p.Pro1310fs) variant causes a frameshift, synonymous 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 Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. PL1310R?) has been classified as Likely pathogenic. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HFM1 NM_001017975.6 frameshift, synonymous
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.190

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]

HFM1 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 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
• PP5: Variant 1-91266061-GG-C is Pathogenic according to our data. Variant chr1-91266061-GG-C is described in ClinVar as [Pathogenic]. Clinvar id is 126431.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HFM1	NM_001017975.6	c.3929_3930delCCinsG	p.Pro1310fs	frameshift_variant, synonymous_variant	36/39	ENST00000370425.8	NP_001017975.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HFM1	ENST00000370425.8	c.3929_3930delCCinsG	p.Pro1310fs	frameshift_variant, synonymous_variant	36/39	1	NM_001017975.6	ENSP00000359454.3
HFM1	ENST00000430465.1	c.1562_1563delCCinsG	p.Pro521fs	frameshift_variant, synonymous_variant	17/19	1		ENSP00000387661.1
HFM1	ENST00000462405.5	n.1809+1683_1809+1684delCCinsG		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Premature ovarian failure 9 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 06, 2014

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs587777270; hg19: chr1-91731618;