NM_020698.4:c.1237A>G

Variant names:

• chr12-94571632-T-C
• rs1169353552
• NM_020698.4:c.1237A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020698.4(TMCC3):​c.1237A>G​(p.Arg413Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMCC3 NM_020698.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.96
• Publications: 0 publications found

Genes affected

TMCC3 (HGNC:29199): (transmembrane and coiled-coil domain family 3) Enables 14-3-3 protein binding activity and identical protein binding activity. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35134947).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020698.4. 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
	TMCC3	NM_020698.4	MANE Select	c.1237A>G	p.Arg413Gly	missense	Exon 4 of 4	NP_065749.3	Q9ULS5
	TMCC3	NM_001301036.2		c.1144A>G	p.Arg382Gly	missense	Exon 4 of 4	NP_001287965.1	G3V207

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCC3	ENST00000261226.9	TSL:1 MANE Select	c.1237A>G	p.Arg413Gly	missense	Exon 4 of 4	ENSP00000261226.4	Q9ULS5
	TMCC3	ENST00000551457.1	TSL:1	c.1144A>G	p.Arg382Gly	missense	Exon 4 of 4	ENSP00000449888.1	G3V207
	TMCC3	ENST00000896389.1		c.1426A>G	p.Arg476Gly	missense	Exon 5 of 5	ENSP00000566448.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.97	L
PhyloP100		8.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.024	B
Vest4		0.22
MutPred		0.69		Loss of methylation at R413 (P = 0.0586)
MVP		0.10
MPC		0.37
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.68
gMVP		0.58
Mutation Taster		=53/47	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: rs1169353552; hg19: chr12-94965408;