3-129828193-C-A

Variant names:

• chr3-129828193-C-A
• rs2058742388
• NM_001017395.5:c.186G>T

Variant summary

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

The NM_001017395.5(TMCC1):​c.186G>T​(p.Arg62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMCC1 NM_001017395.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

Genes affected

TMCC1 (HGNC:29116): (transmembrane and coiled-coil domain family 1) Enables identical protein binding activity. Involved in several processes, including endosome fission; endosome membrane tubulation; and membrane fission. Located in cytosol; endoplasmic reticulum-endosome membrane contact site; and rough endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017395.5. 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
	TMCC1	NM_001017395.5	MANE Select	c.186G>T	p.Arg62Ser	missense	Exon 4 of 7	NP_001017395.2	O94876-1
	TMCC1	NM_001349263.2		c.186G>T	p.Arg62Ser	missense	Exon 5 of 8	NP_001336192.1	O94876-1
	TMCC1	NM_001349264.2		c.186G>T	p.Arg62Ser	missense	Exon 4 of 7	NP_001336193.1	O94876-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCC1	ENST00000393238.8	TSL:1 MANE Select	c.186G>T	p.Arg62Ser	missense	Exon 4 of 7	ENSP00000376930.3	O94876-1
	TMCC1	ENST00000858270.1		c.186G>T	p.Arg62Ser	missense	Exon 5 of 8	ENSP00000528329.1
	TMCC1	ENST00000858271.1		c.186G>T	p.Arg62Ser	missense	Exon 3 of 6	ENSP00000528330.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.22
Sift	Benign	0.39	T
Sift4G	Uncertain	0.011	D
Polyphen		0.98	D
Vest4		0.61
MutPred		0.26		Loss of solvent accessibility (P = 0.0079)
MVP		0.43
MPC		2.1
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.17
gMVP		0.44
Mutation Taster		=58/42	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: rs2058742388; hg19: chr3-129547036;