NM_001258277.2:c.571G>A

Variant names:

• chr6-130440993-G-A
• NM_001258277.2:c.571G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001258277.2(TMEM200A):​c.571G>A​(p.Glu191Lys) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM200A NM_001258277.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.29
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1483106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258277.2. 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
	TMEM200A	NM_001258277.2	MANE Select	c.571G>A	p.Glu191Lys	missense	Exon 3 of 3	NP_001245206.1	Q86VY9
	TMEM200A	NM_001258276.2		c.571G>A	p.Glu191Lys	missense	Exon 2 of 2	NP_001245205.1	Q86VY9
	TMEM200A	NM_001258278.2		c.571G>A	p.Glu191Lys	missense	Exon 2 of 2	NP_001245207.1	Q86VY9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM200A	ENST00000296978.4	TSL:1 MANE Select	c.571G>A	p.Glu191Lys	missense	Exon 3 of 3	ENSP00000296978.3	Q86VY9
	TMEM200A	ENST00000392429.1	TSL:1	c.571G>A	p.Glu191Lys	missense	Exon 2 of 2	ENSP00000376224.1	Q86VY9
	TMEM200A	ENST00000545622.5	TSL:2	c.571G>A	p.Glu191Lys	missense	Exon 2 of 2	ENSP00000438928.1	Q86VY9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.14
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		7.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.036
Sift	Benign	0.046	D
Sift4G	Benign	0.30	T
Polyphen		0.15	B
Vest4		0.36
MutPred		0.38		Gain of ubiquitination at E191 (P = 0.0185)
MVP		0.043
MPC		0.16
ClinPred		0.66	D
GERP RS		4.6
Varity_R		0.12
gMVP		0.60
Mutation Taster		=77/23	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

hg19: chr6-130762138;