X-85327785-T-G

Variant names:

• chrX-85327785-T-G
• rs12557215
• NM_024921.4:c.854+3164A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024921.4(POF1B):​c.854+3164A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 111,478 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
• Consequence: POF1B NM_024921.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

Genes affected

POF1B (HGNC:13711): (POF1B actin binding protein) Premature ovarian failure (POF) is characterized by primary or secondary amenorrhea in women less than 40 years old. Two POF susceptibility regions called "POF1" and "POF2" have been identified by breakpoint mapping of X-autosome translocations. POF1 extends from Xq21-qter while POF2 extends from Xq13.3 to Xq21.1. This gene, POF1B, resides in the POF2 region. This gene is expressed at trace levels in mouse prenatal ovary and is barely detectable or absent from adult ovary, in human and in the mouse respectively. This gene's expression is restricted to epithelia with its highest expression in the epidermis, and oro-pharyngeal and gastro-intestinal tracts. The protein encoded by this gene binds non-muscle actin filaments. The role this gene may play in the etiology of premature ovarian failure remains to be determined. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POF1B	NM_024921.4	c.854+3164A>C		intron_variant	Intron 7 of 16	ENST00000262753.9	NP_079197.3
POF1B	NM_001307940.2	c.854+3164A>C		intron_variant	Intron 7 of 15		NP_001294869.1
POF1B	XM_005262203.5	c.809+3164A>C		intron_variant	Intron 7 of 16		XP_005262260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POF1B	ENST00000262753.9	c.854+3164A>C		intron_variant	Intron 7 of 16	1	NM_024921.4	ENSP00000262753.4
POF1B	ENST00000373145.3	c.854+3164A>C		intron_variant	Intron 7 of 15	1		ENSP00000362238.3

Frequencies

GnomAD3 genomes AF: 0.00000897 AC: 1 AN: 111478 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33698

Gnomad AFR AF: 0.0000328

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: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000897 AC: 1 AN: 111478 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33698

Gnomad4 AFR AF: 0.0000328

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.48

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: rs12557215; hg19: chrX-84582791;