dbSNP rs930173935: TMEM233:p.Ala49Gly (chr12-119593994-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001136534.3(TMEM233):c.146C>G(p.Ala49Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A49V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

TMEM233
NM_001136534.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.69

Variant links:

Genes affected

TMEM233 (HGNC:37219): (transmembrane protein 233) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM233 links:

ENSG00000248636 (HGNC:58183):

ENSG00000248636 links:

LOC105370027 (HGNC:):

LOC105370027 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM233	NM_001136534.3 link	c.146C>G	p.Ala49Gly	missense_variant	Exon 1 of 3	ENST00000426426.3	NP_001130006.1	B4DJY2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM233	ENST00000426426.3 link	c.146C>G	p.Ala49Gly	missense_variant	Exon 1 of 3	2	NM_001136534.3	ENSP00000403130.1		B4DJY2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.53

MetaSVM

Uncertain

0.35

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.31

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.37

MutPred

0.34

Gain of helix (P = 0.2059);

MVP

0.50

ClinPred

0.97

GERP RS

4.1

Varity_R

0.50

gMVP

0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over