9-109057269-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000374586.8(TMEM245):ā€‹c.1776G>Cā€‹(p.Gln592His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

TMEM245
ENST00000374586.8 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.868
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40254635).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM245NM_032012.4 linkuse as main transcriptc.1776G>C p.Gln592His missense_variant 12/18 ENST00000374586.8 NP_114401.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM245ENST00000374586.8 linkuse as main transcriptc.1776G>C p.Gln592His missense_variant 12/181 NM_032012.4 ENSP00000363714 P3Q9H330-2
TMEM245ENST00000413712.7 linkuse as main transcriptc.1752G>C p.Gln584His missense_variant 11/172 ENSP00000394798 A1
TMEM245ENST00000491854.1 linkuse as main transcriptc.*348G>C 3_prime_UTR_variant, NMD_transcript_variant 10/162 ENSP00000417842

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461808
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727206
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsDec 07, 2021The c.1776G>C (p.Q592H) alteration is located in exon 12 (coding exon 12) of the TMEM245 gene. This alteration results from a G to C substitution at nucleotide position 1776, causing the glutamine (Q) at amino acid position 592 to be replaced by a histidine (H). 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
0.16
BayesDel_addAF
Benign
-0.0028
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.40
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
0.98
D
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.12
Sift
Benign
0.56
T
Sift4G
Benign
0.13
T
Polyphen
1.0
D
Vest4
0.51
MutPred
0.24
Gain of catalytic residue at N593 (P = 0.0787);
MVP
0.37
MPC
0.21
ClinPred
0.76
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.099
gMVP
0.66

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.

Other links and lift over

dbSNP: rs1321045416; hg19: chr9-111819549; API