Variant 17-7855088-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203411.2(TMEM88):c.14C>G(p.Pro5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,602,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TMEM88
NM_203411.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0470

Variant links:

Genes affected

TMEM88 (HGNC:32371): (transmembrane protein 88) Predicted to enable PDZ domain binding activity. Involved in negative regulation of canonical Wnt signaling pathway; protein localization to plasma membrane; and protein stabilization. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM88 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.12698302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM88	NM_203411.2 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/2	ENST00000301599.7	NP_981956.1	Q6PEY1
TMEM88	NM_001319941.1 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/2		NP_001306870.1	I3L2J3
TMEM88	XM_005256856.4 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/2		XP_005256913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM88	ENST00000301599.7 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/2	1	NM_203411.2	ENSP00000301599.6		Q6PEY1
TMEM88	ENST00000574668.1 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/2	2		ENSP00000459725.1		I3L2J3

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

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

GnomAD3 exomes

AF:

0.00000845

AC:

AN:

236754

Hom.:

AF XY:

0.00

AC XY:

AN XY:

129470

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1450564

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721870

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.000314

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

Bravo

AF:

0.000128

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.14C>G (p.P5R) alteration is located in exon 1 (coding exon 1) of the TMEM88 gene. This alteration results from a C to G substitution at nucleotide position 14, causing the proline (P) at amino acid position 5 to be replaced by an arginine (R). 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

Benign

0.081

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0068

T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.045

Sift

Uncertain

0.019

D;.

Sift4G

Benign

0.076

T;D

Polyphen

0.34

B;.

Vest4

0.48

MVP

0.33

MPC

0.031

ClinPred

0.096

GERP RS

2.6

Varity_R

0.070

gMVP

0.52

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over