Variant 9-109050645-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_032012.4(TMEM245):c.1902G>C(p.Leu634=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,613,152 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00031 ( 1 hom. )

Consequence

TMEM245
NM_032012.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.634

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 -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 9-109050645-C-G is Benign according to our data. Variant chr9-109050645-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2659407.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.634 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM245	NM_032012.4 linkuse as main transcript	c.1902G>C	p.Leu634=	synonymous_variant	13/18	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.1902G>C	p.Leu634=	synonymous_variant	13/18	1	NM_032012.4	ENSP00000363714	P3	Q9H330-2
TMEM245	ENST00000413712.7 linkuse as main transcript	c.1878G>C	p.Leu626=	synonymous_variant	12/17	2		ENSP00000394798	A1
TMEM245	ENST00000491854.1 linkuse as main transcript	c.*474G>C		3_prime_UTR_variant, NMD_transcript_variant	11/16	2		ENSP00000417842

Frequencies

GnomAD3 genomes

AF:

0.000211

AC:

AN:

151346

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000727

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000236

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.000562

AC:

140

AN:

249280

Hom.:

AF XY:

0.000518

AC XY:

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000557

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000313

AC:

457

AN:

1461806

Hom.:

Cov.:

AF XY:

0.000304

AC XY:

221

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.000524

Gnomad4 NFE exome

AF:

0.000257

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000211

AC:

AN:

151346

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

AN XY:

73822

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.000727

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000191

Gnomad4 NFE

AF:

0.000236

Gnomad4 OTH

AF:

0.000483

Alfa

AF:

0.000380

Hom.:

Bravo

AF:

0.000298

EpiCase

AF:

0.000872

EpiControl

AF:

0.000948

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

TMEM245: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.27

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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