rs201350921

Variant names:

• chr16-8796055-C-G
• rs201350921
• NM_015421.4:c.539G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-8796055-C-G
• chr16-8796055-C-T

Variant summary

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

The NM_015421.4(TMEM186):​c.539G>C​(p.Arg180Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM186 NM_015421.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807

Genes affected

TMEM186 (HGNC:24530): (transmembrane protein 186) This gene encodes a potential transmembrane protein. [provided by RefSeq, Dec 2012]

PMM2 (HGNC:9115): (phosphomannomutase 2) The protein encoded by this gene catalyzes the isomerization of mannose 6-phosphate to mannose 1-phosphate, which is a precursor to GDP-mannose necessary for the synthesis of dolichol-P-oligosaccharides. Mutations in this gene have been shown to cause defects in glycoprotein biosynthesis, which manifests as carbohydrate-deficient glycoprotein syndrome type I. [provided by RefSeq, Jul 2008]

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=0.2834501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM186	NM_015421.4	c.539G>C	p.Arg180Pro	missense_variant	Exon 2 of 2	ENST00000333050.7	NP_056236.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM186	ENST00000333050.7	c.539G>C	p.Arg180Pro	missense_variant	Exon 2 of 2	1	NM_015421.4	ENSP00000331640.6
PMM2	ENST00000566983.5	c.-15-5744C>G		intron_variant	Intron 1 of 7	5		ENSP00000457956.1
TMEM186	ENST00000564869.1	n.31+1557G>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	0.0085	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.16
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.012	D
Polyphen		0.92	P
Vest4		0.44
MutPred		0.46		Loss of MoRF binding (P = 7e-04);
MVP		0.13
MPC		0.14
ClinPred		0.90	D
GERP RS		1.6
Varity_R		0.58
gMVP		0.86

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: rs201350921; hg19: chr16-8889912;