rs1671760038

Variant names:

• chr1-29121267-T-A
• rs1671760038
• NM_001003682.4:c.562A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001003682.4(TMEM200B):​c.562A>T​(p.Ile188Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,459,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TMEM200B NM_001003682.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045829207).

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.562A>T	p.Ile188Phe	missense	Exon 2 of 2	NP_001003682.1	Q69YZ2
	TMEM200B	NM_001171868.2		c.562A>T	p.Ile188Phe	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.562A>T	p.Ile188Phe	missense	Exon 2 of 2	ENSP00000428459.1	Q69YZ2
	TMEM200B	ENST00000420504.2	TSL:1	c.562A>T	p.Ile188Phe	missense	Exon 2 of 2	ENSP00000428544.1	Q69YZ2
	TMEM200B	ENST00000870613.1		c.562A>T	p.Ile188Phe	missense	Exon 3 of 3	ENSP00000540672.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1459538 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725928

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111548

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 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	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.060
Sift	Benign	0.055	T
Sift4G	Benign	0.41	T
Polyphen		0.0060	B
Vest4		0.074
MutPred		0.14		Loss of sheet (P = 0.1907)
MVP		0.030
MPC		1.3
ClinPred		0.068	T
GERP RS		3.5
Varity_R		0.12
gMVP		0.21
Mutation Taster		=96/4	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: rs1671760038; hg19: chr1-29447779;