15-72407790-C-A

Variant names:

• chr15-72407790-C-A
• rs146051533
• NM_001080462.3:c.719C>A

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.719C>A​(p.Pro240Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. P240L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM202 NM_001080462.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973
• 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=0.26158845).

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.719C>A	p.Pro240Gln	missense	Exon 5 of 5	NP_001073931.1	A6NGA9
	TMEM202-AS1	NR_135678.1		n.741G>T		non_coding_transcript_exon	Exon 4 of 4
	TMEM202	NR_148418.2		n.485C>A		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM202	ENST00000341689.4	TSL:5 MANE Select	c.719C>A	p.Pro240Gln	missense	Exon 5 of 5	ENSP00000340212.3	A6NGA9
	TMEM202	ENST00000649825.1		c.386C>A	p.Pro129Gln	missense	Exon 5 of 5	ENSP00000497819.1	A0A3B3ITB0
	TMEM202	ENST00000567679.1	TSL:2	c.*145C>A		3_prime_UTR	Exon 3 of 3	ENSP00000456083.1	H3BUG9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.032
Eigen_PC	Benign	-0.096
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.97
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.17
Sift	Benign	0.077	T
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.19		Loss of phosphorylation at T242 (P = 0.0851)
MVP		0.33
MPC		0.48
ClinPred		0.97	D
GERP RS		3.4
Varity_R		0.073
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs146051533; hg19: chr15-72700131;