rs12557804

Variant names:

• chrX-85278402-G-A
• rs12557804
• NM_024921.4:c.*1019C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-85278402-G-A
• chrX-85278402-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024921.4(POF1B):​c.*1019C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 109,699 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes 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 0.00011 (0 hom., 2 hem., cov: 22)
• Consequence: POF1B NM_024921.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328
• Publications: 1 publications found

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]

POF1B Gene-Disease associations (from GenCC):

• premature ovarian failure 2B

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POF1B	NM_024921.4	c.*1019C>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000262753.9	NP_079197.3
POF1B	XM_005262203.5	c.*1019C>T		3_prime_UTR_variant	Exon 17 of 17		XP_005262260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POF1B	ENST00000262753.9	c.*1019C>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_024921.4	ENSP00000262753.4

Frequencies

GnomAD3 genomes AF: 0.000109 AC: 12 AN: 109699 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000966

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: 0.000191

Gnomad OTH AF: 0.000681

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.000109 AC: 12 AN: 109699 Hom.: 0 Cov.: 22 AF XY: 0.0000620 AC XY: 2 AN XY: 32263

African (AFR) AF: 0.00 AC: 0 AN: 30212

American (AMR) AF: 0.0000966 AC: 1 AN: 10354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2607

East Asian (EAS) AF: 0.00 AC: 0 AN: 3442

South Asian (SAS) AF: 0.00 AC: 0 AN: 2626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.000191 AC: 10 AN: 52244

Other (OTH) AF: 0.000681 AC: 1 AN: 1469

Alfa AF: 0.00 Hom.: 3185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		0.33

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: rs12557804; hg19: chrX-84533408;