X-85277572-C-T

Position:

• chrX-85277572-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024921.4(POF1B):​c.*1849G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 110,074 control chromosomes in the GnomAD database, including 828 homozygotes. There are 2,442 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (828 hom., 2442 hem., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: POF1B NM_024921.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.638

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant X-85277572-C-T is Benign according to our data. Variant chrX-85277572-C-T is described in ClinVar as [Benign]. Clinvar id is 368759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POF1B	NM_024921.4	c.*1849G>A		3_prime_UTR_variant	17/17	ENST00000262753.9	NP_079197.3
POF1B	XM_005262203.5	c.*1849G>A		3_prime_UTR_variant	17/17		XP_005262260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POF1B	ENST00000262753	c.*1849G>A		3_prime_UTR_variant	17/17	1	NM_024921.4	ENSP00000262753.4

Frequencies

GnomAD3 genomes AF: 0.0817 AC: 8990 AN: 110027 Hom.: 828 Cov.: 22 AF XY: 0.0743 AC XY: 2420 AN XY: 32553

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.000762

Gnomad EAS AF: 0.0213

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.00252

Gnomad MID AF: 0.0216

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.0693

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0819 AC: 9012 AN: 110074 Hom.: 828 Cov.: 22 AF XY: 0.0749 AC XY: 2442 AN XY: 32610

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.0617

Gnomad4 ASJ AF: 0.000762

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.0238

Gnomad4 FIN AF: 0.00252

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.0685

Alfa AF: 0.0503 Hom.: 256

Bravo AF: 0.0941

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Premature ovarian failure 2B Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Non-syndromic X-linked intellectual disability Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.78
DANN	Benign	0.57

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: rs73513629; hg19: chrX-84532578;