chr7-130672770-G-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_052933.4(TSGA13):​c.494C>T​(p.Ser165Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

TSGA13
NM_052933.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.157

Publications

3 publications found
Variant links:
Genes affected
TSGA13 (HGNC:12369): (testis specific 13)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.008550853).
BP6
Variant 7-130672770-G-A is Benign according to our data. Variant chr7-130672770-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2562473.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSGA13NM_052933.4 linkc.494C>T p.Ser165Leu missense_variant Exon 6 of 8 ENST00000356588.8 NP_443165.1 Q96PP4A0A024R769
TSGA13NM_001304968.2 linkc.494C>T p.Ser165Leu missense_variant Exon 7 of 9 NP_001291897.1 Q96PP4A0A024R769

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSGA13ENST00000356588.8 linkc.494C>T p.Ser165Leu missense_variant Exon 6 of 8 1 NM_052933.4 ENSP00000348996.3 Q96PP4
TSGA13ENST00000456951.5 linkc.494C>T p.Ser165Leu missense_variant Exon 7 of 9 2 ENSP00000406047.1 Q96PP4

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
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
GnomAD2 exomes
AF:
0.0000716
AC:
18
AN:
251314
AF XY:
0.0000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00139
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000595
AC:
87
AN:
1461734
Hom.:
0
Cov.:
31
AF XY:
0.0000633
AC XY:
46
AN XY:
727166
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33468
American (AMR)
AF:
0.00
AC:
0
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
0.00149
AC:
39
AN:
26132
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39684
South Asian (SAS)
AF:
0.0000696
AC:
6
AN:
86228
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000315
AC:
35
AN:
1111944
Other (OTH)
AF:
0.0000994
AC:
6
AN:
60380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.464
Heterozygous variant carriers
0
5
10
16
21
26
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152286
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74462
show subpopulations
African (AFR)
AF:
0.0000481
AC:
2
AN:
41562
American (AMR)
AF:
0.000131
AC:
2
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.00115
AC:
4
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68016
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.481
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000148
Hom.:
0
Bravo
AF:
0.0000529
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Benign:1
Apr 18, 2023
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
0.079
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.13
DANN
Benign
0.61
DEOGEN2
Benign
0.016
T;T
Eigen
Benign
-1.9
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0020
N
LIST_S2
Benign
0.46
.;T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.0086
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.42
N;N
PhyloP100
-0.16
PrimateAI
Benign
0.28
T
PROVEAN
Benign
1.9
N;N
REVEL
Benign
0.0020
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
B;B
Vest4
0.12
MVP
0.030
MPC
0.27
ClinPred
0.033
T
GERP RS
-4.0
Varity_R
0.024
gMVP
0.041
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs199718973; hg19: chr7-130357610; COSMIC: COSV58404223; COSMIC: COSV58404223; API