Variant 9-109060428-C-A 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_032012.4(TMEM245):c.1648G>T(p.Val550Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 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:

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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=0.16551295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM245	NM_032012.4 linkuse as main transcript	c.1648G>T	p.Val550Leu	missense_variant	11/18	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.1648G>T	p.Val550Leu	missense_variant	11/18	1	NM_032012.4	ENSP00000363714	P3	Q9H330-2
TMEM245	ENST00000413712.7 linkuse as main transcript	c.1624G>T	p.Val542Leu	missense_variant	10/17	2		ENSP00000394798	A1
TMEM245	ENST00000491854.1 linkuse as main transcript	c.*220G>T		3_prime_UTR_variant, NMD_transcript_variant	9/16	2		ENSP00000417842

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248542

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460660

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726634

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

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

Jan 07, 2022

The c.1648G>T (p.V550L) alteration is located in exon 11 (coding exon 11) of the TMEM245 gene. This alteration results from a G to T substitution at nucleotide position 1648, causing the valine (V) at amino acid position 550 to be replaced by a leucine (L). 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

0.24

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.12

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.010

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.84

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.1

REVEL

Benign

0.037

Sift

Benign

0.13

Sift4G

Benign

0.17

Polyphen

0.0090

Vest4

0.41

MutPred

0.28

Loss of loop (P = 0.0603);

MVP

0.061

MPC

0.22

ClinPred

0.12

GERP RS

-0.18

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.053

gMVP

0.54

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