rs12933482

Variant names:

• chr16-72155705-A-G
• rs12933482
• NM_031293.3:c.166-1246T>C

Variant summary

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

The NM_031293.3(PMFBP1):​c.166-1246T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 152,292 control chromosomes in the GnomAD database, including 451 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 0.069 (451 hom., cov: 32)
• Consequence: PMFBP1 NM_031293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMFBP1	NM_031293.3	c.166-1246T>C		intron_variant	Intron 3 of 20	ENST00000237353.15	NP_112583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMFBP1	ENST00000237353.15	c.166-1246T>C		intron_variant	Intron 3 of 20	1	NM_031293.3	ENSP00000237353.10

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10520 AN: 152174 Hom.: 452 Cov.: 32

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.0454

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0690 AC: 10515 AN: 152292 Hom.: 451 Cov.: 32 AF XY: 0.0656 AC XY: 4887 AN XY: 74480

African (AFR) AF: 0.0322 AC: 1337 AN: 41570

American (AMR) AF: 0.0650 AC: 994 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 281 AN: 3472

East Asian (EAS) AF: 0.0455 AC: 236 AN: 5186

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4828

European-Finnish (FIN) AF: 0.0557 AC: 591 AN: 10616

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0982 AC: 6681 AN: 68016

Other (OTH) AF: 0.0677 AC: 143 AN: 2112

Alfa AF: 0.0913 Hom.: 825

Bravo AF: 0.0694

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	14
DANN	Benign	0.65
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs12933482; hg19: chr16-72189604;