rs1238320199

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-40251361-C-A
• chr1-40251361-C-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>A​(p.Pro106Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMCO2 NM_001008740.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.13084656).

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>A	p.Pro106Thr	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>A	p.Pro106Thr	missense	Exon 2 of 2	ENSP00000361852.3	Q7Z6W1
	TMCO2	ENST00000468258.1	TSL:3	n.229C>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461782 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111974

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Benign	0.091
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.49
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.070
Sift	Uncertain	0.012	D
Sift4G	Benign	0.083	T
Polyphen		0.57	P
Vest4		0.29
MutPred		0.28		Loss of disorder (P = 0.122)
MVP		0.040
MPC		0.93
ClinPred		0.97	D
GERP RS		1.7
Varity_R		0.27
gMVP		0.18
Mutation Taster		=88/12	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;