Variant 9-109057284-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032012.4(TMEM245):c.1761G>T(p.Leu587Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,613,988 control chromosomes in the GnomAD database, including 2 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 2 hom. )

Consequence

TMEM245
NM_032012.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.056902736).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM245	NM_032012.4 linkuse as main transcript	c.1761G>T	p.Leu587Phe	missense_variant	12/18	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.1761G>T	p.Leu587Phe	missense_variant	12/18	1	NM_032012.4	ENSP00000363714	P3	Q9H330-2
TMEM245	ENST00000413712.7 linkuse as main transcript	c.1737G>T	p.Leu579Phe	missense_variant	11/17	2		ENSP00000394798	A1
TMEM245	ENST00000491854.1 linkuse as main transcript	c.*333G>T		3_prime_UTR_variant, NMD_transcript_variant	10/16	2		ENSP00000417842

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000333

AC:

AN:

249418

Hom.:

AF XY:

0.000296

AC XY:

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000495

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000272

AC:

397

AN:

1461782

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

211

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000275

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000283

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000418

Hom.:

Bravo

AF:

0.000306

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000484

AC:

ExAC

AF:

0.000397

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000948

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

Jul 27, 2021

The c.1761G>T (p.L587F) alteration is located in exon 12 (coding exon 12) of the TMEM245 gene. This alteration results from a G to T substitution at nucleotide position 1761, causing the leucine (L) at amino acid position 587 to be replaced by a phenylalanine (F). 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

0.072

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.069

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

M_CAP

Benign

0.0078

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.96

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.1

REVEL

Benign

0.028

Sift

Benign

0.068

Sift4G

Benign

0.16

Polyphen

0.047

Vest4

0.31

MutPred

0.25

Gain of methylation at K586 (P = 0.0275);

MVP

0.17

MPC

0.25

ClinPred

0.066

GERP RS

4.6

Varity_R

0.15

gMVP

0.32

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