1-29120951-C-T

Variant names:

• chr1-29120951-C-T
• rs763361864
• NM_001003682.4:c.878G>A

Variant summary

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

The NM_001003682.4(TMEM200B):​c.878G>A​(p.Gly293Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMEM200B NM_001003682.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.919
• Publications: 0 publications found

Genes affected

TMEM200B (HGNC:33785): (transmembrane protein 200B) Predicted to be integral component of membrane. [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=0.2333529).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003682.4. 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
	TMEM200B	NM_001003682.4	MANE Select	c.878G>A	p.Gly293Asp	missense	Exon 2 of 2	NP_001003682.1	Q69YZ2
	TMEM200B	NM_001171868.2		c.878G>A	p.Gly293Asp	missense	Exon 2 of 2	NP_001165339.1	Q69YZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM200B	ENST00000521452.2	TSL:1 MANE Select	c.878G>A	p.Gly293Asp	missense	Exon 2 of 2	ENSP00000428459.1	Q69YZ2
	TMEM200B	ENST00000420504.2	TSL:1	c.878G>A	p.Gly293Asp	missense	Exon 2 of 2	ENSP00000428544.1	Q69YZ2
	TMEM200B	ENST00000870613.1		c.878G>A	p.Gly293Asp	missense	Exon 3 of 3	ENSP00000540672.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000807 AC: 2 AN: 247808 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460042 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726170

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111154

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152314 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74468

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

ExAC AF: 0.00000824 AC: 1

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	0.38
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.92
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.41		Loss of sheet (P = 0.0126)
MVP		0.18
MPC		1.1
ClinPred		0.28	T
GERP RS		4.3
Varity_R		0.35
gMVP		0.25
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: rs763361864; hg19: chr1-29447463;