6-130441152-C-G

Variant names:

• chr6-130441152-C-G
• rs201003025
• NM_001258277.2:c.730C>G

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.730C>G​(p.Pro244Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. P244S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM200A NM_001258277.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94

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=0.21743482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM200A	NM_001258277.2	c.730C>G	p.Pro244Ala	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.730C>G	p.Pro244Ala	missense_variant	Exon 3 of 3	1	NM_001258277.2	ENSP00000296978.3
TMEM200A	ENST00000392429.1	c.730C>G	p.Pro244Ala	missense_variant	Exon 2 of 2	1		ENSP00000376224.1
TMEM200A	ENST00000545622.5	c.730C>G	p.Pro244Ala	missense_variant	Exon 2 of 2	2		ENSP00000438928.1
TMEM200A	ENST00000617887.4	c.730C>G	p.Pro244Ala	missense_variant	Exon 2 of 2	2		ENSP00000480294.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461758 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727186

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111950

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.25	T;T;T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.72	.;.;T;.
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.55	N;N;N;N
PhyloP100		3.9
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.5	D;.;D;D
REVEL	Benign	0.11
Sift	Benign	0.39	T;.;T;T
Sift4G	Benign	0.44	T;T;T;T
Polyphen		0.95	P;P;P;P
Vest4		0.21
MutPred		0.24		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP		0.093
MPC		0.18
ClinPred		0.70	D
GERP RS		5.9
Varity_R		0.093
gMVP		0.21
Mutation Taster		=73/27	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

Publications

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Other links and lift over

dbSNP: rs201003025; hg19: chr6-130762297;