chr7-130671678-C-G

Variant names:

• chr7-130671678-C-G
• rs782262457
• NM_052933.4:c.641G>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.641G>C​(p.Arg214Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,978 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. 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. R214K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TSGA13 NM_052933.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 0 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=0.12847987).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052933.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSGA13	NM_052933.4	MANE Select	c.641G>C	p.Arg214Thr	missense	Exon 7 of 8	NP_443165.1	Q96PP4
	TSGA13	NM_001304968.2		c.641G>C	p.Arg214Thr	missense	Exon 8 of 9	NP_001291897.1	Q96PP4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSGA13	ENST00000356588.8	TSL:1 MANE Select	c.641G>C	p.Arg214Thr	missense	Exon 7 of 8	ENSP00000348996.3	Q96PP4
	TSGA13	ENST00000456951.5	TSL:2	c.641G>C	p.Arg214Thr	missense	Exon 8 of 9	ENSP00000406047.1	Q96PP4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442978 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718156

African (AFR) AF: 0.00 AC: 0 AN: 32834

American (AMR) AF: 0.00 AC: 0 AN: 44084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25502

East Asian (EAS) AF: 0.00 AC: 0 AN: 38982

South Asian (SAS) AF: 0.00 AC: 0 AN: 83820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52706

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5626

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100158

Other (OTH) AF: 0.00 AC: 0 AN: 59266

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.11
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.010
Sift	Benign	0.083	T
Sift4G	Benign	0.11	T
Polyphen		0.19	B
Vest4		0.38
MutPred		0.25		Loss of MoRF binding (P = 0.0164)
MVP		0.12
MPC		0.32
ClinPred		0.19	T
GERP RS		2.4
Varity_R		0.13
gMVP		0.18
Mutation Taster		=93/7	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: rs782262457; hg19: chr7-130356518;