rs1399671765

Variant names:

• chr15-72406740-G-A
• rs1399671765
• NM_001080462.3:c.476G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-72406740-G-A
• chr15-72406740-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080462.3(TMEM202):​c.476G>A​(p.Ser159Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: TMEM202 NM_001080462.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0440
• Publications: 0 publications found

Genes affected

TMEM202 (HGNC:33733): (transmembrane protein 202) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM202-AS1 (HGNC:53265): (TMEM202 antisense RNA 1)

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=0.24758923).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080462.3. 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
	TMEM202	NM_001080462.3	MANE Select	c.476G>A	p.Ser159Asn	missense	Exon 3 of 5	NP_001073931.1	A6NGA9
	TMEM202	NR_148418.2		n.242G>A		non_coding_transcript_exon	Exon 2 of 4
	TMEM202	NR_148419.2		n.242G>A		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM202	ENST00000341689.4	TSL:5 MANE Select	c.476G>A	p.Ser159Asn	missense	Exon 3 of 5	ENSP00000340212.3	A6NGA9
	TMEM202	ENST00000649825.1		c.143G>A	p.Ser48Asn	missense	Exon 3 of 5	ENSP00000497819.1	A0A3B3ITB0
	TMEM202	ENST00000567679.1	TSL:2	c.*34G>A		3_prime_UTR	Exon 2 of 3	ENSP00000456083.1	H3BUG9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251304 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461812 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727218

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

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111964

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000731 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.044
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.14
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.012	D
Polyphen		0.95	P
Vest4		0.47
MutPred		0.30		Loss of ubiquitination at K154 (P = 0.1066)
MVP		0.33
MPC		0.34
ClinPred		0.73	D
GERP RS		2.4
Varity_R		0.12
gMVP		0.24
Mutation Taster		=94/6	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: rs1399671765; hg19: chr15-72699081;