chr1-29121531-C-G

Variant names:

• chr1-29121531-C-G
• rs1180996483
• NM_001003682.4:c.298G>C

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.298G>C​(p.Glu100Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000037 in 1,351,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000037 (0 hom.)
• Consequence: TMEM200B NM_001003682.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08
• 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=0.24546418).

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.298G>C	p.Glu100Gln	missense	Exon 2 of 2	NP_001003682.1	Q69YZ2
	TMEM200B	NM_001171868.2		c.298G>C	p.Glu100Gln	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.298G>C	p.Glu100Gln	missense	Exon 2 of 2	ENSP00000428459.1	Q69YZ2
	TMEM200B	ENST00000420504.2	TSL:1	c.298G>C	p.Glu100Gln	missense	Exon 2 of 2	ENSP00000428544.1	Q69YZ2
	TMEM200B	ENST00000870613.1		c.298G>C	p.Glu100Gln	missense	Exon 3 of 3	ENSP00000540672.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000988 AC: 1 AN: 101168 AF XY: 0.0000176

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000255

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000370 AC: 5 AN: 1351322 Hom.: 0 Cov.: 31 AF XY: 0.00000451 AC XY: 3 AN XY: 665828

African (AFR) AF: 0.00 AC: 0 AN: 28892

American (AMR) AF: 0.00 AC: 0 AN: 28972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23302

East Asian (EAS) AF: 0.00 AC: 0 AN: 34302

South Asian (SAS) AF: 0.00 AC: 0 AN: 75704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5192

European-Non Finnish (NFE) AF: 0.00000469 AC: 5 AN: 1065932

Other (OTH) AF: 0.00 AC: 0 AN: 56188

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

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	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.026
Eigen_PC	Benign	-0.083
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.070	N
REVEL	Benign	0.099
Sift	Benign	0.28	T
Sift4G	Benign	0.095	T
Polyphen		0.94	P
Vest4		0.11
MutPred		0.64		Gain of MoRF binding (P = 0.0522)
MVP		0.12
MPC		0.93
ClinPred		0.23	T
GERP RS		1.8
Varity_R		0.13
gMVP		0.45
Mutation Taster		=89/11	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: rs1180996483; hg19: chr1-29448043;