chr1-40251361-C-T

Variant names:

• chr1-40251361-C-T
• rs1238320199
• NM_001008740.4:c.316C>T

Variant summary

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

The NM_001008740.4(TMCO2):​c.316C>T​(p.Pro106Ser) 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. 15/21 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. P106T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMCO2 NM_001008740.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490
• Publications: 0 publications found

Genes affected

TMCO2 (HGNC:23312): (transmembrane and coiled-coil domains 2) Located in nucleus. [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=0.07336345).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008740.4. 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
	TMCO2	NM_001008740.4	MANE Select	c.316C>T	p.Pro106Ser	missense	Exon 2 of 2	NP_001008740.1	A0A140VKB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCO2	ENST00000372766.4	TSL:1 MANE Select	c.316C>T	p.Pro106Ser	missense	Exon 2 of 2	ENSP00000361852.3	Q7Z6W1
	TMCO2	ENST00000468258.1	TSL:3	n.229C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.49
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.033
Sift	Benign	0.092	T
Sift4G	Benign	0.21	T
Polyphen		0.035	B
Vest4		0.26
MutPred		0.22		Gain of disorder (P = 0.0818)
MVP		0.030
MPC		0.85
ClinPred		0.57	D
GERP RS		1.7
Varity_R		0.11
gMVP		0.21
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: rs1238320199; hg19: chr1-40717033;