16-72118856-T-C

Variant names:

• chr16-72118856-T-C
• rs8044555
• ENST00000537792.5:c.266+4058A>G

Variant summary

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

The ENST00000537792.5(PMFBP1):​c.266+4058A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,072 control chromosomes in the GnomAD database, including 6,663 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 0.29 (6663 hom., cov: 32)
• Consequence: PMFBP1 ENST00000537792.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000537792.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMFBP1	NM_031293.3	MANE Select	c.*482A>G		downstream_gene	N/A	NP_112583.2
	PMFBP1	NM_001160213.2		c.*482A>G		downstream_gene	N/A	NP_001153685.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMFBP1	ENST00000537792.5	TSL:2	c.266+4058A>G		intron	N/A	ENSP00000443366.1
	PMFBP1	ENST00000237353.15	TSL:1 MANE Select	c.*482A>G		downstream_gene	N/A	ENSP00000237353.10
	PMFBP1	ENST00000537465.5	TSL:2	c.*948A>G		downstream_gene	N/A	ENSP00000443817.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43766 AN: 151954 Hom.: 6660 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.288 AC: 43788 AN: 152072 Hom.: 6663 Cov.: 32 AF XY: 0.286 AC XY: 21298 AN XY: 74358

African (AFR) AF: 0.386 AC: 16003 AN: 41456

American (AMR) AF: 0.236 AC: 3612 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 991 AN: 3472

East Asian (EAS) AF: 0.286 AC: 1478 AN: 5172

South Asian (SAS) AF: 0.403 AC: 1938 AN: 4814

European-Finnish (FIN) AF: 0.214 AC: 2267 AN: 10578

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16563 AN: 67982

Other (OTH) AF: 0.301 AC: 634 AN: 2104

Alfa AF: 0.235 Hom.: 2368

Bravo AF: 0.289

Asia WGS AF: 0.328 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.81
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs8044555; hg19: chr16-72152755;