12-117046810-G-C

Variant names:

• chr12-117046810-G-C
• NM_017899.4:c.378C>G
• TESC p.Ser126Arg

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.378C>G​(p.Ser126Arg) 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. 12/17 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. S126G) 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: 0.200
• Publications: 0 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=0.10501781).

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.378C>G	p.Ser126Arg	missense	Exon 5 of 8	NP_060369.3	Q96BS2-1
	TESC	NM_001168325.2		c.297C>G	p.Ser99Arg	missense	Exon 4 of 7	NP_001161797.1	Q96BS2-3
	TESC	NR_031766.3		n.512C>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.378C>G	p.Ser126Arg	missense	Exon 5 of 8	ENSP00000334785.7	Q96BS2-1
	TESC	ENST00000940881.1		c.378C>G	p.Ser126Arg	missense	Exon 5 of 8	ENSP00000610940.1
	TESC	ENST00000874651.1		c.378C>G	p.Ser126Arg	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	0.48
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.20
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.15
Sift	Benign	0.12	T
PromoterAI		-0.064	Neutral
Varity_R		0.047
Mutation Taster		=63/37	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-117484615;