12-117046803-G-C

Variant names:

• chr12-117046803-G-C
• rs979997799
• NM_017899.4:c.385C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017899.4(TESC):​c.385C>G​(p.Arg129Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 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. R129C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TESC NM_017899.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• Publications: 3 publications found

Genes affected

TESC (HGNC:26065): (tescalcin) Enables calcium ion binding activity. Involved in several processes, including cellular response to retinoic acid; positive regulation of macromolecule metabolic process; and positive regulation of myeloid cell differentiation. Located in several cellular components, including cytosol; lamellipodium; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18724951).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017899.4. 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
	TESC	NM_017899.4	MANE Select	c.385C>G	p.Arg129Gly	missense	Exon 5 of 8	NP_060369.3	Q96BS2-1
	TESC	NM_001168325.2		c.304C>G	p.Arg102Gly	missense	Exon 4 of 7	NP_001161797.1	Q96BS2-3
	TESC	NR_031766.3		n.519C>G		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESC	ENST00000335209.12	TSL:1 MANE Select	c.385C>G	p.Arg129Gly	missense	Exon 5 of 8	ENSP00000334785.7	Q96BS2-1
	TESC	ENST00000940881.1		c.385C>G	p.Arg129Gly	missense	Exon 5 of 8	ENSP00000610940.1
	TESC	ENST00000874651.1		c.385C>G	p.Arg129Gly	missense	Exon 5 of 7	ENSP00000544710.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.091
Eigen_PC	Benign	0.0086
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.75	T
PhyloP100		3.0
PROVEAN	Benign	1.2	N
REVEL	Benign	0.050
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
MutPred		0.28		Gain of catalytic residue at R15 (P = 0.0067)
MVP		0.093
ClinPred		0.81	D
GERP RS		3.8
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
Mutation Taster		=88/12	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: rs979997799; hg19: chr12-117484608;