17-50518617-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032133.6(MYCBPAP):​c.545C>T​(p.Pro182Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MYCBPAP
NM_032133.6 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.720
Variant links:
Genes affected
MYCBPAP (HGNC:19677): (MYCBP associated protein) Involved in spermatogenesis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18846932).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYCBPAPNM_032133.6 linkc.545C>T p.Pro182Leu missense_variant Exon 5 of 19 ENST00000323776.11 NP_115509.5 Q8TBZ2A0A140VK87B4DZQ1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYCBPAPENST00000323776.11 linkc.545C>T p.Pro182Leu missense_variant Exon 5 of 19 1 NM_032133.6 ENSP00000323184.6 Q8TBZ2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000806
AC:
2
AN:
248214
Hom.:
0
AF XY:
0.00000745
AC XY:
1
AN XY:
134308
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000110
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1458314
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725628
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.674C>T (p.P225L) alteration is located in exon 5 (coding exon 5) of the MYCBPAP gene. This alteration results from a C to T substitution at nucleotide position 674, causing the proline (P) at amino acid position 225 to be replaced by a leucine (L). 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
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.079
.;.;T
Eigen
Benign
0.037
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.74
.;T;.
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-3.9
D;D;D
REVEL
Benign
0.060
Sift
Uncertain
0.0060
D;D;D
Sift4G
Benign
0.20
T;T;D
Vest4
0.19
MutPred
0.20
Loss of glycosylation at P188 (P = 0.013);.;.;
MVP
0.48
MPC
0.20
ClinPred
0.58
D
GERP RS
2.3

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: rs765590088; hg19: chr17-48595978; API