Variant 7-130683672-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_052933.4(TSGA13):c.24G>C(p.Lys8Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,613,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

TSGA13
NM_052933.4 missense, splice_region

Scores

Splicing: ADA: 0.03734

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.212

Variant links:

Genes affected

TSGA13 (HGNC:12369): (testis specific 13)

TSGA13 links:

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=0.08386183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSGA13	NM_052933.4 linkuse as main transcript	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	3/8	ENST00000356588.8	NP_443165.1
TSGA13	NM_001304968.2 linkuse as main transcript	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	4/9		NP_001291897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TSGA13	ENST00000356588.8 linkuse as main transcript	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	3/8	1	NM_052933.4	ENSP00000348996	P1
TSGA13	ENST00000456951.5 linkuse as main transcript	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	4/9	2		ENSP00000406047	P1
TSGA13	ENST00000443954.5 linkuse as main transcript	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	4/6	4		ENSP00000415856
TSGA13	ENST00000438346.1 linkuse as main transcript	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	4/5	5		ENSP00000407352

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000956

AC:

AN:

251150

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000931

AC:

136

AN:

1461336

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000447

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

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 submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.24G>C (p.K8N) alteration is located in exon 3 (coding exon 2) of the TSGA13 gene. This alteration results from a G to C substitution at nucleotide position 24, causing the lysine (K) at amino acid position 8 to be replaced by an asparagine (N). 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

0.20

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T;.;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.45

.;T;T;T

MetaRNN

Benign

0.084

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;.;.

MutationTaster

Benign

0.93

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

N;N;D;D

REVEL

Benign

0.021

Sift

Uncertain

0.010

D;D;D;D

Sift4G

Uncertain

0.012

D;D;.;D

Polyphen

0.25

B;B;.;.

Vest4

0.14

MutPred

0.24

Loss of methylation at K8 (P = 6e-04);Loss of methylation at K8 (P = 6e-04);Loss of methylation at K8 (P = 6e-04);Loss of methylation at K8 (P = 6e-04);

MVP

0.16

MPC

0.36

ClinPred

0.056

GERP RS

2.7

Varity_R

0.23

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.037

dbscSNV1_RF

Benign

0.50

SpliceAI score (max)

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over