chr11-123883200-C-T

Variant names:

• chr11-123883200-C-T
• rs1273013840
• NM_001013743.3:c.616G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013743.3(TMEM225):​c.616G>A​(p.Ala206Thr) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM225 NM_001013743.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.26
• Publications: 0 publications found

Genes affected

TMEM225 (HGNC:32390): (transmembrane protein 225) Predicted to be involved in negative regulation of phosphatase activity. Predicted to be located in acrosomal membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043388367).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013743.3. 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
	TMEM225	NM_001013743.3	MANE Select	c.616G>A	p.Ala206Thr	missense	Exon 4 of 4	NP_001013765.2	Q6GV28
	TMEM225	NM_001363605.2		c.466G>A	p.Ala156Thr	missense	Exon 4 of 4	NP_001350534.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM225	ENST00000375026.7	TSL:1 MANE Select	c.616G>A	p.Ala206Thr	missense	Exon 4 of 4	ENSP00000364166.2	Q6GV28
	TMEM225	ENST00000528595.1	TSL:3	c.*15G>A		downstream_gene	N/A	ENSP00000431282.1	E9PLT9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	Benign	0.074
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0020
DANN	Benign	0.83
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0033	N
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.1	T
PhyloP100		-2.3
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.023
Sift	Benign	0.35	T
Sift4G	Benign	0.41	T
Vest4		0.056
MutPred		0.23		Gain of sheet (P = 0.0125)
MVP		0.068
MPC		0.12
ClinPred		0.14	T
GERP RS		-7.3
gMVP		0.030
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: rs1273013840; hg19: chr11-123753907;