15-72406649-A-C

Variant names:

• chr15-72406649-A-C
• NM_001080462.3:c.385A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080462.3(TMEM202):​c.385A>C​(p.Ile129Leu) 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 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM202 NM_001080462.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089010715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM202	NM_001080462.3	c.385A>C	p.Ile129Leu	missense_variant	Exon 3 of 5	ENST00000341689.4	NP_001073931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM202	ENST00000341689.4	c.385A>C	p.Ile129Leu	missense_variant	Exon 3 of 5	5	NM_001080462.3	ENSP00000340212.3
TMEM202	ENST00000649825.1	c.52A>C	p.Ile18Leu	missense_variant	Exon 3 of 5			ENSP00000497819.1
TMEM202	ENST00000567679.1	c.129A>C	p.Pro43Pro	synonymous_variant	Exon 2 of 3	2		ENSP00000456083.1
TMEM202	ENST00000568167.5	n.129A>C		non_coding_transcript_exon_variant	Exon 2 of 4	2		ENSP00000457632.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461720 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727168

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: 8.99e-7

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	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.77
DEOGEN2	Benign	0.0069	T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.59	N;.
REVEL	Benign	0.058
Sift	Benign	0.19	T;.
Sift4G	Benign	0.91	T;.
Polyphen		0.21	B;.
Vest4		0.39
MutPred		0.37		Loss of MoRF binding (P = 0.2733);.;
MVP		0.061
MPC		0.20
ClinPred		0.098	T
GERP RS		1.7
Varity_R		0.056
gMVP		0.40

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-72698990;