XM_047434734.1:c.-863+9964G>A

Variant names:

• chr16-72190436-C-T
• rs12918956
• XM_047434734.1:c.-863+9964G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047434734.1(PMFBP1):​c.-863+9964G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,098 control chromosomes in the GnomAD database, including 23,020 homozygotes. 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 0.55 (23020 hom., cov: 33)
• Consequence: PMFBP1 XM_047434734.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• Publications: 17 publications found

Genes affected

PMFBP1 (HGNC:17728): (polyamine modulated factor 1 binding protein 1) Involved in spermatogenesis. Located in sperm connecting piece. Implicated in spermatogenic failure 31. [provided by Alliance of Genome Resources, Apr 2022]

PMFBP1 Gene-Disease associations (from GenCC):

• spermatogenic failure 31

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.546 AC: 83031 AN: 151980 Hom.: 22995 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.546 AC: 83103 AN: 152098 Hom.: 23020 Cov.: 33 AF XY: 0.544 AC XY: 40448 AN XY: 74354

African (AFR) AF: 0.608 AC: 25199 AN: 41478

American (AMR) AF: 0.443 AC: 6767 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2351 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1751 AN: 5168

South Asian (SAS) AF: 0.637 AC: 3076 AN: 4830

European-Finnish (FIN) AF: 0.536 AC: 5663 AN: 10564

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.538 AC: 36613 AN: 67996

Other (OTH) AF: 0.544 AC: 1149 AN: 2112

Alfa AF: 0.539 Hom.: 12500

Bravo AF: 0.537

Asia WGS AF: 0.505 AC: 1760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.65
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs12918956; hg19: chr16-72224335;