11-123885346-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001013743.3(TMEM225):​c.80G>T​(p.Gly27Val) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TMEM225
NM_001013743.3 missense

Scores

6
3
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM225NM_001013743.3 linkc.80G>T p.Gly27Val missense_variant Exon 1 of 4 ENST00000375026.7 NP_001013765.2
TMEM225XM_011542802.4 linkc.80G>T p.Gly27Val missense_variant Exon 1 of 3 XP_011541104.1
TMEM225NM_001363605.2 linkc.31+49G>T intron_variant Intron 1 of 3 NP_001350534.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM225ENST00000375026.7 linkc.80G>T p.Gly27Val missense_variant Exon 1 of 4 1 NM_001013743.3 ENSP00000364166.2 Q6GV28
TMEM225ENST00000528595.1 linkc.31+49G>T intron_variant Intron 1 of 3 3 ENSP00000431282.1 E9PLT9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 13, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.80G>T (p.G27V) alteration is located in exon 1 (coding exon 1) of the TMEM225 gene. This alteration results from a G to T substitution at nucleotide position 80, causing the glycine (G) at amino acid position 27 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.56
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.010
CADD
Benign
22
DANN
Uncertain
0.99
Eigen
Benign
0.11
Eigen_PC
Benign
-0.025
FATHMM_MKL
Benign
0.18
N
M_CAP
Benign
0.024
T
MetaRNN
Pathogenic
0.75
D
MetaSVM
Benign
-0.34
T
PrimateAI
Benign
0.39
T
PROVEAN
Pathogenic
-8.0
D
REVEL
Uncertain
0.35
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Vest4
0.84
MutPred
0.36
Gain of sheet (P = 0.0061);
MVP
0.80
MPC
0.63
ClinPred
1.0
D
GERP RS
4.9
gMVP
0.34

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: chr11-123756053; API