Variant 9-109087265-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032012.4(TMEM245):c.1228A>G(p.Ile410Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,614,036 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

TMEM245
NM_032012.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.593

Variant links:

Genes affected

TMEM245 (HGNC:1363): (transmembrane protein 245) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM245 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040679187).

BP6

Variant 9-109087265-T-C is Benign according to our data. Variant chr9-109087265-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2373014.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM245	NM_032012.4 linkuse as main transcript	c.1228A>G	p.Ile410Val	missense_variant	6/18	ENST00000374586.8	NP_114401.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM245	ENST00000374586.8 linkuse as main transcript	c.1228A>G	p.Ile410Val	missense_variant	6/18	1	NM_032012.4	ENSP00000363714	P3	Q9H330-2
TMEM245	ENST00000413712.7 linkuse as main transcript	c.1228A>G	p.Ile410Val	missense_variant	6/17	2		ENSP00000394798	A1
TMEM245	ENST00000491854.1 linkuse as main transcript	c.478A>G	p.Ile160Val	missense_variant, NMD_transcript_variant	5/16	2		ENSP00000417842

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000401

AC:

AN:

249374

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

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:

0.0000530

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.42

DANN

Benign

0.19

DEOGEN2

Benign

0.047

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.21

M_CAP

Benign

0.0030

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.15

REVEL

Benign

0.065

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.086

MVP

0.048

MPC

0.18

ClinPred

0.028

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.013

gMVP

0.24

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