Genetic Variant TMEM245:p.Leu634Leu (chr9-109050645-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_032012.4(TMEM245):c.1902G>C(p.Leu634Leu) 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

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.029).

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 rank	MANE	Protein	UniProt
TMEM245	NM_032012.4 link	c.1902G>C	p.Leu634Leu	synonymous_variant	Exon 13 of 18	ENST00000374586.8	NP_114401.2	Q9H330-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM245	ENST00000374586.8 link	c.1902G>C	p.Leu634Leu	synonymous_variant	Exon 13 of 18	1	NM_032012.4	ENSP00000363714.3	Q9H330-2
TMEM245	ENST00000413712.7 link	c.1878G>C	p.Leu626Leu	synonymous_variant	Exon 12 of 17	2		ENSP00000394798.3	H7C0G1
TMEM245	ENST00000491854.1 link	n.*474G>C		non_coding_transcript_exon_variant	Exon 11 of 16	2		ENSP00000417842.1	F8WBJ7
TMEM245	ENST00000491854.1 link	n.*474G>C		3_prime_UTR_variant	Exon 11 of 16	2		ENSP00000417842.1	F8WBJ7

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

GnomAD2 exomes

AF:

0.000562

AC:

140

AN:

249280

AF XY:

0.000518

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 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

African (AFR)

AF:

0.0000597

AC:

AN:

33474

American (AMR)

AF:

0.00136

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000927

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000524

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000257

AC:

286

AN:

1111966

Other (OTH)

AF:

0.000464

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000211

AC:

AN:

151346

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

AN XY:

73822

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41152

American (AMR)

AF:

0.000727

AC:

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4742

European-Finnish (FIN)

AF:

0.000191

AC:

AN:

10488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000236

AC:

AN:

67918

Other (OTH)

AF:

0.000483

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TMEM245: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.27

(source)

DANN

Benign

0.72

PhyloP100

-0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

polymorphism

(source)

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

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9-109050645-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over