6-130440993-G-A

Position:

• chr6-130440993-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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: TMEM200A NM_001258277.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.29

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 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=0.1483106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM200A	NM_001258277.2	c.571G>A	p.Glu191Lys	missense_variant	3/3	ENST00000296978.4	NP_001245206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM200A	ENST00000296978.4	c.571G>A	p.Glu191Lys	missense_variant	3/3	1	NM_001258277.2	ENSP00000296978	P1
TMEM200A	ENST00000392429.1	c.571G>A	p.Glu191Lys	missense_variant	2/2	1		ENSP00000376224	P1
TMEM200A	ENST00000545622.5	c.571G>A	p.Glu191Lys	missense_variant	2/2	2		ENSP00000438928	P1
TMEM200A	ENST00000617887.4	c.571G>A	p.Glu191Lys	missense_variant	2/2	2		ENSP00000480294	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 19, 2022

The c.571G>A (p.E191K) alteration is located in exon 2 (coding exon 1) of the TMEM200A gene. This alteration results from a G to A substitution at nucleotide position 571, causing the glutamic acid (E) at amino acid position 191 to be replaced by a lysine (K). 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	0.12
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T;T;T;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;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.78	N;.;N;N
REVEL	Benign	0.036
Sift	Benign	0.046	D;.;D;D
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.15	B;B;B;B
Vest4		0.36
MutPred		0.38		Gain of ubiquitination at E191 (P = 0.0185);Gain of ubiquitination at E191 (P = 0.0185);Gain of ubiquitination at E191 (P = 0.0185);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

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: chr6-130762138;