rs543455233

Variant names:

• chr18-5890866-T-G
• rs543455233
• NM_001395400.1:c.1198A>C

Your query was ambiguous. Multiple possible variants found:

• chr18-5890866-T-G
• chr18-5890866-T-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001395400.1(TMEM200C):​c.1198A>C​(p.Ser400Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 682,132 control chromosomes in the GnomAD database, including 12 homozygotes. 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S400I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0027 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (9 hom.)
• Consequence: TMEM200C NM_001395400.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.389
• Publications: 1 publications found

Genes affected

TMEM200C (HGNC:37208): (transmembrane protein 200C) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000264449 (HGNC:):

MIR3976HG (HGNC:51104): (MIR3976 host gene)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0051736534).
• BP6: Variant 18-5890866-T-G is Benign according to our data. Variant chr18-5890866-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2648536.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395400.1. 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
	TMEM200C	NM_001395400.1	MANE Select	c.1198A>C	p.Ser400Arg	missense	Exon 2 of 2	NP_001382329.1	A6NKL6
	TMEM200C	NM_001080209.3		c.1198A>C	p.Ser400Arg	missense	Exon 3 of 3	NP_001073678.1	A6NKL6
	MIR3976HG	NR_172496.1		n.1405+1693T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM200C	ENST00000383490.3	TSL:6 MANE Select	c.1198A>C	p.Ser400Arg	missense	Exon 2 of 2	ENSP00000372982.2	A6NKL6
	TMEM200C	ENST00000581347.2	TSL:5	c.1198A>C	p.Ser400Arg	missense	Exon 3 of 3	ENSP00000463375.1	A6NKL6
	TMEM200C	ENST00000930047.1		c.1198A>C	p.Ser400Arg	missense	Exon 2 of 2	ENSP00000600106.1

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 408 AN: 151750 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00345

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00224 AC: 249 AN: 110966 AF XY: 0.00225

Gnomad AFR exome AF: 0.000299

Gnomad AMR exome AF: 0.000456

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0130

Gnomad NFE exome AF: 0.00344

Gnomad OTH exome AF: 0.00205

GnomAD4 exome AF: 0.00307 AC: 1630 AN: 530276 Hom.: 9 Cov.: 0 AF XY: 0.00278 AC XY: 801 AN XY: 287834

African (AFR) AF: 0.000603 AC: 8 AN: 13268

American (AMR) AF: 0.000668 AC: 22 AN: 32914

Ashkenazi Jewish (ASJ) AF: 0.000103 AC: 2 AN: 19402

East Asian (EAS) AF: 0.00 AC: 0 AN: 29742

South Asian (SAS) AF: 0.00102 AC: 62 AN: 60774

European-Finnish (FIN) AF: 0.0140 AC: 463 AN: 33058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3238

European-Non Finnish (NFE) AF: 0.00318 AC: 981 AN: 308068

Other (OTH) AF: 0.00309 AC: 92 AN: 29812

GnomAD4 genome AF: 0.00269 AC: 408 AN: 151856 Hom.: 3 Cov.: 32 AF XY: 0.00311 AC XY: 231 AN XY: 74258

African (AFR) AF: 0.000530 AC: 22 AN: 41530

American (AMR) AF: 0.000786 AC: 12 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.0129 AC: 135 AN: 10432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00345 AC: 234 AN: 67876

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00148 Hom.: 1

Bravo AF: 0.00172

ExAC AF: 0.000554 AC: 18

Asia WGS AF: 0.000583 AC: 2 AN: 3446

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.39
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.021
Sift	Benign	0.033	D
Sift4G	Uncertain	0.049	D
Polyphen		0.14	B
Vest4		0.12
MutPred		0.23		Loss of phosphorylation at S400 (P = 0.0292)
MVP		0.055
ClinPred		0.027	T
GERP RS		-0.56
Varity_R		0.17
gMVP		0.19
Mutation Taster		=100/0	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: rs543455233; hg19: chr18-5890865;