1-29121491-C-T

Variant names:

• chr1-29121491-C-T
• NM_001003682.4:c.338G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001003682.4(TMEM200B):​c.338G>A​(p.Arg113Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000218 in 1,373,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R113L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: TMEM200B NM_001003682.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.35

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3048845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM200B	NM_001003682.4	c.338G>A	p.Arg113Gln	missense_variant	Exon 2 of 2	ENST00000521452.2	NP_001003682.1
TMEM200B	NM_001171868.2	c.338G>A	p.Arg113Gln	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.338G>A	p.Arg113Gln	missense_variant	Exon 2 of 2	1	NM_001003682.4	ENSP00000428459.1
TMEM200B	ENST00000420504.2	c.338G>A	p.Arg113Gln	missense_variant	Exon 2 of 2	1		ENSP00000428544.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000218 AC: 3 AN: 1373690 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 676826

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000280

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T;T
Eigen	Benign	-0.099
Eigen_PC	Benign	-0.093
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.67	.;T
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.39
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.044	D;D
Polyphen		0.63	P;P
Vest4		0.20
MutPred		0.68		Loss of MoRF binding (P = 0.0352);Loss of MoRF binding (P = 0.0352);
MVP		0.13
MPC		1.9
ClinPred		0.78	D
GERP RS		2.7
Varity_R		0.22
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-29448003;