6-130441048-C-A

Variant names:

• chr6-130441048-C-A
• rs145944902
• NM_001258277.2:c.626C>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.626C>A​(p.Thr209Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,596 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. T209R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM200A NM_001258277.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.82
• 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=0.22042564).

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.626C>A	p.Thr209Lys	missense	Exon 3 of 3	NP_001245206.1	Q86VY9
	TMEM200A	NM_001258276.2		c.626C>A	p.Thr209Lys	missense	Exon 2 of 2	NP_001245205.1	Q86VY9
	TMEM200A	NM_001258278.2		c.626C>A	p.Thr209Lys	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.626C>A	p.Thr209Lys	missense	Exon 3 of 3	ENSP00000296978.3	Q86VY9
	TMEM200A	ENST00000392429.1	TSL:1	c.626C>A	p.Thr209Lys	missense	Exon 2 of 2	ENSP00000376224.1	Q86VY9
	TMEM200A	ENST00000545622.5	TSL:2	c.626C>A	p.Thr209Lys	missense	Exon 2 of 2	ENSP00000438928.1	Q86VY9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250426 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461596 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727108

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111918

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.010
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.8
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.14
Sift	Benign	0.045	D
Sift4G	Benign	0.93	T
Polyphen		0.42	B
Vest4		0.49
MutPred		0.48		Gain of MoRF binding (P = 0.0446)
MVP		0.082
MPC		0.22
ClinPred		0.49	T
GERP RS		4.7
Varity_R		0.19
gMVP		0.52
Mutation Taster		=66/34	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: rs145944902; hg19: chr6-130762193;