rs116944106

Variant names:

• chr7-130671672-A-T
• rs116944106
• NM_052933.4:c.647T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_052933.4(TSGA13):​c.647T>A​(p.Met216Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,580,832 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: TSGA13 NM_052933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.49
• Publications: 1 publications found

Genes affected

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.04296574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSGA13	NM_052933.4	c.647T>A	p.Met216Lys	missense_variant	Exon 7 of 8	ENST00000356588.8	NP_443165.1
TSGA13	NM_001304968.2	c.647T>A	p.Met216Lys	missense_variant	Exon 8 of 9		NP_001291897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSGA13	ENST00000356588.8	c.647T>A	p.Met216Lys	missense_variant	Exon 7 of 8	1	NM_052933.4	ENSP00000348996.3
TSGA13	ENST00000456951.5	c.647T>A	p.Met216Lys	missense_variant	Exon 8 of 9	2		ENSP00000406047.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000331 AC: 8 AN: 241780 AF XY: 0.0000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000725

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000121 AC: 173 AN: 1428610 Hom.: 0 Cov.: 30 AF XY: 0.000113 AC XY: 80 AN XY: 711100

African (AFR) AF: 0.0000309 AC: 1 AN: 32382

American (AMR) AF: 0.00 AC: 0 AN: 43316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25116

East Asian (EAS) AF: 0.00 AC: 0 AN: 38398

South Asian (SAS) AF: 0.00 AC: 0 AN: 81784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 0.000155 AC: 169 AN: 1091490

Other (OTH) AF: 0.0000514 AC: 3 AN: 58384

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74420

African (AFR) AF: 0.0000241 AC: 1 AN: 41540

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.647T>A (p.M216K) alteration is located in exon 7 (coding exon 6) of the TSGA13 gene. This alteration results from a T to A substitution at nucleotide position 647, causing the methionine (M) at amino acid position 216 to be replaced by a lysine (K). 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	0.082
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.030
DANN	Benign	0.57
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.27	.;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N;N
PhyloP100		-1.5
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.023
Sift	Benign	0.31	T;T
Sift4G	Uncertain	0.052	T;T
Polyphen		0.0010	B;B
Vest4		0.29
MVP		0.11
MPC		0.17
ClinPred		0.061	T
GERP RS		-11
Varity_R		0.19
gMVP		0.18
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116944106; hg19: chr7-130356512;