rs17668704

Variant names:

• chr16-72223800-A-T
• rs17668704
• XM_047434734.1:c.-1010-23253T>A

Variant summary

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

The ENST00000731624.1(ENSG00000295660):​n.382+162T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,078 control chromosomes in the GnomAD database, including 8,700 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 0.33 (8700 hom., cov: 32)
• Consequence: ENSG00000295660 ENST00000731624.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 7 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)

ENSG00000295660 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000731624.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000295660	ENST00000731624.1		n.382+162T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50071 AN: 151960 Hom.: 8674 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.330 AC: 50145 AN: 152078 Hom.: 8700 Cov.: 32 AF XY: 0.333 AC XY: 24772 AN XY: 74348

African (AFR) AF: 0.364 AC: 15108 AN: 41464

American (AMR) AF: 0.232 AC: 3548 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1303 AN: 3470

East Asian (EAS) AF: 0.106 AC: 549 AN: 5176

South Asian (SAS) AF: 0.478 AC: 2306 AN: 4824

European-Finnish (FIN) AF: 0.414 AC: 4377 AN: 10580

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21906 AN: 67980

Other (OTH) AF: 0.314 AC: 663 AN: 2110

Alfa AF: 0.325 Hom.: 1011

Bravo AF: 0.311

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.86
PhyloP100		-0.028

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17668704;

hg19: chr16-72257699;