rs12933482

Positions:

• chr16-72155705-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PMFBP1	NM_031293.3	c.166-1246T>C		intron_variant		ENST00000237353.15	NP_112583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMFBP1	ENST00000237353.15	c.166-1246T>C		intron_variant		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

Gnomad4 AFR AF: 0.0322

Gnomad4 AMR AF: 0.0650

Gnomad4 ASJ AF: 0.0809

Gnomad4 EAS AF: 0.0455

Gnomad4 SAS AF: 0.0408

Gnomad4 FIN AF: 0.0557

Gnomad4 NFE AF: 0.0982

Gnomad4 OTH AF: 0.0677

Alfa AF: 0.0953 Hom.: 698

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

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: rs12933482; hg19: chr16-72189604;