16-72119342-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031293.3(PMFBP1):​c.3020G>A​(p.Cys1007Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

PMFBP1
NM_031293.3 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0150
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058817893).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PMFBP1NM_031293.3 linkc.3020G>A p.Cys1007Tyr missense_variant 21/21 ENST00000237353.15 NP_112583.2 Q8TBY8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PMFBP1ENST00000237353.15 linkc.3020G>A p.Cys1007Tyr missense_variant 21/211 NM_031293.3 ENSP00000237353.10 Q8TBY8-2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251450
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461764
Hom.:
0
Cov.:
30
AF XY:
0.0000138
AC XY:
10
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.000364
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000384
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.00375
AC:
13
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 18, 2023The c.3020G>A (p.C1007Y) alteration is located in exon 21 (coding exon 20) of the PMFBP1 gene. This alteration results from a G to A substitution at nucleotide position 3020, causing the cysteine (C) at amino acid position 1007 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
14
DANN
Benign
0.89
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.059
T;T
MetaSVM
Benign
-0.97
T
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.63
N;N
REVEL
Benign
0.075
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.69
P;.
Vest4
0.30
MutPred
0.31
Gain of phosphorylation at C1007 (P = 0.0463);.;
MVP
0.16
MPC
0.39
ClinPred
0.49
T
GERP RS
0.039
gMVP
0.028

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370319198; hg19: chr16-72153241; COSMIC: COSV105865622; API