chr1-29121516-C-T

Variant names:

• chr1-29121516-C-T
• rs1671780367
• NM_001003682.4:c.313G>A

Variant summary

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

The NM_001003682.4(TMEM200B):​c.313G>A​(p.Gly105Ser) 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. 13/20 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)
• Consequence: TMEM200B NM_001003682.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.196

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=0.1564872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM200B	NM_001003682.4	c.313G>A	p.Gly105Ser	missense_variant	Exon 2 of 2	ENST00000521452.2	NP_001003682.1
TMEM200B	NM_001171868.2	c.313G>A	p.Gly105Ser	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.313G>A	p.Gly105Ser	missense_variant	Exon 2 of 2	1	NM_001003682.4	ENSP00000428459.1
TMEM200B	ENST00000420504.2	c.313G>A	p.Gly105Ser	missense_variant	Exon 2 of 2	1		ENSP00000428544.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.313G>A (p.G105S) alteration is located in exon 2 (coding exon 1) of the TMEM200B gene. This alteration results from a G to A substitution at nucleotide position 313, causing the glycine (G) at amino acid position 105 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.0036	T;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.58	.;T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.25	N;N
REVEL	Benign	0.11
Sift	Benign	0.45	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.25	B;B
Vest4		0.26
MutPred		0.40		Gain of phosphorylation at G105 (P = 0.0051);Gain of phosphorylation at G105 (P = 0.0051);
MVP		0.040
MPC		1.0
ClinPred		0.17	T
GERP RS		3.0
Varity_R		0.078
gMVP		0.41

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: rs1671780367; hg19: chr1-29448028;