6-130440810-C-G

Variant names:

• chr6-130440810-C-G
• NM_001258277.2:c.388C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001258277.2(TMEM200A):​c.388C>G​(p.Pro130Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM200A NM_001258277.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.86

Genes affected

TMEM200A (HGNC:21075): (transmembrane protein 200A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM200A	NM_001258277.2	c.388C>G	p.Pro130Ala	missense_variant	Exon 3 of 3	ENST00000296978.4	NP_001245206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM200A	ENST00000296978.4	c.388C>G	p.Pro130Ala	missense_variant	Exon 3 of 3	1	NM_001258277.2	ENSP00000296978.3
TMEM200A	ENST00000392429.1	c.388C>G	p.Pro130Ala	missense_variant	Exon 2 of 2	1		ENSP00000376224.1
TMEM200A	ENST00000545622.5	c.388C>G	p.Pro130Ala	missense_variant	Exon 2 of 2	2		ENSP00000438928.1
TMEM200A	ENST00000617887.4	c.388C>G	p.Pro130Ala	missense_variant	Exon 2 of 2	2		ENSP00000480294.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.388C>G (p.P130A) alteration is located in exon 2 (coding exon 1) of the TMEM200A gene. This alteration results from a C to G substitution at nucleotide position 388, causing the proline (P) at amino acid position 130 to be replaced by an alanine (A). 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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;D;D;D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;.;D;.
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.96	D;D;D;D
MetaSVM	Uncertain	-0.025	T
MutationAssessor	Pathogenic	3.1	M;M;M;M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-8.0	D;.;D;D
REVEL	Pathogenic	0.72
Sift	Pathogenic	0.0	D;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.82
MutPred		0.84		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.61
MPC		0.62
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.79
gMVP		0.91

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: chr6-130761955;