chr7-130669159-C-A

Variant names:

• chr7-130669159-C-A
• rs1796184651
• NM_052933.4:c.683G>T

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.683G>T​(p.Arg228Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R228K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TSGA13 NM_052933.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40
• 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=0.03586492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSGA13	NM_052933.4	c.683G>T	p.Arg228Met	missense_variant	Exon 8 of 8	ENST00000356588.8	NP_443165.1
TSGA13	NM_001304968.2	c.683G>T	p.Arg228Met	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.683G>T	p.Arg228Met	missense_variant	Exon 8 of 8	1	NM_052933.4	ENSP00000348996.3
TSGA13	ENST00000456951.5	c.683G>T	p.Arg228Met	missense_variant	Exon 9 of 9	2		ENSP00000406047.1
ENSG00000287547	ENST00000667779.1	n.308C>A		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.016
DANN	Benign	0.88
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.18	.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;N
PhyloP100		-3.4
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.024
Sift	Benign	0.10	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.0090	B;B
Vest4		0.12
MutPred		0.16		Loss of MoRF binding (P = 0.0202);Loss of MoRF binding (P = 0.0202);
MVP		0.030
MPC		0.39
ClinPred		0.10	T
GERP RS		-11
PromoterAI		-0.091	Neutral
Varity_R		0.039
gMVP		0.16
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1796184651; hg19: chr7-130353999;