rs1309763643

Variant names:

• chr1-29121296-G-A
• rs1309763643
• NM_001003682.4:c.533C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-29121296-G-A
• chr1-29121296-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003682.4(TMEM200B):​c.533C>T​(p.Pro178Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. P178H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: TMEM200B NM_001003682.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.100432366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM200B	NM_001003682.4	c.533C>T	p.Pro178Leu	missense_variant	Exon 2 of 2	ENST00000521452.2	NP_001003682.1
TMEM200B	NM_001171868.2	c.533C>T	p.Pro178Leu	missense_variant	Exon 2 of 2		NP_001165339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM200B	ENST00000521452.2	c.533C>T	p.Pro178Leu	missense_variant	Exon 2 of 2	1	NM_001003682.4	ENSP00000428459.1
TMEM200B	ENST00000420504.2	c.533C>T	p.Pro178Leu	missense_variant	Exon 2 of 2	1		ENSP00000428544.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152162 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74326

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.63	.;T
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.072
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.0010	B;B
Vest4		0.11
MutPred		0.17		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.11
MPC		2.0
ClinPred		0.38	T
GERP RS		2.5
Varity_R		0.068
gMVP		0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs1309763643; hg19: chr1-29447808;