rs201003025

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-130441152-C-A
• chr6-130441152-C-G
• chr6-130441152-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001258277.2(TMEM200A):​c.730C>A​(p.Pro244Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000021 (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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30447283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM200A	NM_001258277.2	c.730C>A	p.Pro244Thr	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>A	p.Pro244Thr	missense_variant	Exon 3 of 3	1	NM_001258277.2	ENSP00000296978.3
TMEM200A	ENST00000392429.1	c.730C>A	p.Pro244Thr	missense_variant	Exon 2 of 2	1		ENSP00000376224.1
TMEM200A	ENST00000545622.5	c.730C>A	p.Pro244Thr	missense_variant	Exon 2 of 2	2		ENSP00000438928.1
TMEM200A	ENST00000617887.4	c.730C>A	p.Pro244Thr	missense_variant	Exon 2 of 2	2		ENSP00000480294.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250510 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135394

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461758 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	0.0025	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;T;T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	.;.;T;.
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.90	L;L;L;L
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.9	D;.;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D;.;D;D
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.99	D;D;D;D
Vest4		0.42
MutPred		0.22		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		0.082
MPC		0.22
ClinPred		0.73	D
GERP RS		5.9
Varity_R		0.23
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs201003025; hg19: chr6-130762297; COSMIC: COSV51660162;