6-36400538-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152990.4(PXT1):​c.216G>C​(p.Lys72Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PXT1
NM_152990.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0940
Variant links:
Genes affected
PXT1 (HGNC:18312): (peroxisomal testis enriched protein 1) Predicted to be involved in positive regulation of apoptotic process. Predicted to act upstream of or within spermatogenesis. Predicted to be active in nucleus and peroxisome. [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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.017946333).
BP6
Variant 6-36400538-C-G is Benign according to our data. Variant chr6-36400538-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3311852.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PXT1NM_152990.4 linkc.216G>C p.Lys72Asn missense_variant Exon 4 of 5 ENST00000454782.3 NP_694535.2 Q8NFP0
PXT1XM_011514400.3 linkc.231G>C p.Lys77Asn missense_variant Exon 3 of 4 XP_011512702.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PXT1ENST00000454782.3 linkc.216G>C p.Lys72Asn missense_variant Exon 4 of 5 1 NM_152990.4 ENSP00000419944.1 Q8NFP0

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152150
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:
0.000192
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:
0.0000557
AC:
14
AN:
251430
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000761
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:
0.00000958
AC:
14
AN:
1461654
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727120
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000302
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
May 02, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
6.8
DANN
Benign
0.44
DEOGEN2
Benign
0.00078
T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.0020
N
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.69
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
2.1
N
REVEL
Benign
0.064
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Vest4
0.14
MutPred
0.24
Loss of methylation at K72 (P = 0.0015);
MVP
0.048
MPC
0.0022
ClinPred
0.020
T
GERP RS
0.32
Varity_R
0.059
gMVP
0.0083

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: rs758302235; hg19: chr6-36368315; API