chr16-72226794-G-A

Variant names:

• chr16-72226794-G-A
• rs811047
• XM_047434734.1:c.-1011+22369C>T

Variant summary

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

The XM_047434734.1(PMFBP1):​c.-1011+22369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,870 control chromosomes in the GnomAD database, including 22,158 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 0.52 (22158 hom., cov: 32)
• Consequence: PMFBP1 XM_047434734.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 5 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79675 AN: 151752 Hom.: 22151 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.525 AC: 79696 AN: 151870 Hom.: 22158 Cov.: 32 AF XY: 0.525 AC XY: 38948 AN XY: 74220

African (AFR) AF: 0.332 AC: 13717 AN: 41366

American (AMR) AF: 0.644 AC: 9836 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2031 AN: 3470

East Asian (EAS) AF: 0.750 AC: 3875 AN: 5168

South Asian (SAS) AF: 0.458 AC: 2196 AN: 4800

European-Finnish (FIN) AF: 0.548 AC: 5768 AN: 10516

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40464 AN: 67956

Other (OTH) AF: 0.567 AC: 1199 AN: 2114

Alfa AF: 0.581 Hom.: 115619

Bravo AF: 0.529

Asia WGS AF: 0.586 AC: 2038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.66
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs811047; hg19: chr16-72260693;