chr7-130669168-G-T

Variant names:

• chr7-130669168-G-T
• rs200223001
• NM_052933.4:c.674C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052933.4(TSGA13):​c.674C>A​(p.Ala225Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,156 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 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TSGA13 NM_052933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.58
• Publications: 0 publications found

Genes affected

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

ENSG00000287547 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022553205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSGA13	NM_052933.4	c.674C>A	p.Ala225Glu	missense_variant	Exon 8 of 8	ENST00000356588.8	NP_443165.1
TSGA13	NM_001304968.2	c.674C>A	p.Ala225Glu	missense_variant	Exon 9 of 9		NP_001291897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSGA13	ENST00000356588.8	c.674C>A	p.Ala225Glu	missense_variant	Exon 8 of 8	1	NM_052933.4	ENSP00000348996.3
TSGA13	ENST00000456951.5	c.674C>A	p.Ala225Glu	missense_variant	Exon 9 of 9	2		ENSP00000406047.1
ENSG00000287547	ENST00000667779.1	n.317G>T		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251352 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

African (AFR) AF: 0.0000896 AC: 3 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74462

African (AFR) AF: 0.0000962 AC: 4 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.674C>A (p.A225E) alteration is located in exon 8 (coding exon 7) of the TSGA13 gene. This alteration results from a C to A substitution at nucleotide position 674, causing the alanine (A) at amino acid position 225 to be replaced by a glutamic acid (E). 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	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.063
DANN	Benign	0.75
DEOGEN2	Benign	0.016	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.30	.;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.023	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.20	N;N
PhyloP100		-4.6
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.81	N;N
REVEL	Benign	0.070
Sift	Benign	0.69	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0030	B;B
Vest4		0.048
MVP		0.030
MPC		0.49
ClinPred		0.034	T
GERP RS		-11
PromoterAI		-0.0068	Neutral
Varity_R		0.074
gMVP		0.11
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs200223001; hg19: chr7-130354008;