16-72118856-T-C

Position:

• chr16-72118856-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMFBP1	XM_011523357.4	c.3082+995A>G		intron_variant			XP_011521659.1
PMFBP1	XM_011523358.4	c.3082+995A>G		intron_variant			XP_011521660.1
PMFBP1	XM_011523360.4	c.3082+995A>G		intron_variant			XP_011521662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMFBP1	ENST00000537792.5	c.266+4058A>G		intron_variant		2		ENSP00000443366.1

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

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.301

Alfa AF: 0.234 Hom.: 2125

Bravo AF: 0.289

Asia WGS AF: 0.328 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8044555; hg19: chr16-72152755;