chr7-130683672-C-G

Variant names:

• chr7-130683672-C-G
• rs149851433
• NM_052933.4:c.24G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 15/22 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
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 rank	MANE	Protein	UniProt
TSGA13	NM_052933.4	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	Exon 3 of 8	ENST00000356588.8	NP_443165.1
TSGA13	NM_001304968.2	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	Exon 4 of 9		NP_001291897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSGA13	ENST00000356588.8	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	Exon 3 of 8	1	NM_052933.4	ENSP00000348996.3
TSGA13	ENST00000456951.5	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	Exon 4 of 9	2		ENSP00000406047.1
TSGA13	ENST00000443954.5	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	Exon 4 of 6	4		ENSP00000415856.1
TSGA13	ENST00000438346.1	c.24G>C	p.Lys8Asn	missense_variant, splice_region_variant	Exon 4 of 5	5		ENSP00000407352.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152148 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.0000956 AC: 24 AN: 251150 AF XY: 0.000111

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 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.: 0 Cov.: 30 AF XY: 0.000105 AC XY: 76 AN XY: 726970

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.0000448 AC: 2 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000116 AC: 129 AN: 1111678

Other (OTH) AF: 0.0000663 AC: 4 AN: 60374

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152148 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74324

African (AFR) AF: 0.0000483 AC: 2 AN: 41436

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68042

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000447 Hom.: 0

Bravo AF: 0.0000718

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;.;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.45	.;T;T;T
MetaRNN	Benign	0.084	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.;.
PhyloP100		0.21
PrimateAI	Benign	0.31	T
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	T
GERP RS		2.7
Varity_R		0.23
gMVP		0.19
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs149851433; hg19: chr7-130368510;