Variant chr19-11345594-C-G 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_198536.3(TMEM205):c.26G>C(p.Gly9Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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)

Consequence

TMEM205
NM_198536.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.610

Variant links:

Genes affected

TMEM205 (HGNC:29631): (transmembrane protein 205) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM205 links:

CCDC159 (HGNC:26996): (coiled-coil domain containing 159)

CCDC159 links:

RAB3D (HGNC:9779): (RAB3D, member RAS oncogene family) Enables myosin V binding activity. Involved in bone resorption and positive regulation of regulated secretory pathway. Located in cytoplasmic microtubule and secretory vesicle. [provided by Alliance of Genome Resources, Apr 2022]

RAB3D 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=0.07520649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM205	NM_198536.3 linkuse as main transcript	c.26G>C	p.Gly9Ala	missense_variant	1/3	ENST00000354882.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM205	ENST00000354882.10 linkuse as main transcript	c.26G>C	p.Gly9Ala	missense_variant	1/3	1	NM_198536.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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 25, 2023

The c.26G>C (p.G9A) alteration is located in exon 1 (coding exon 1) of the TMEM205 gene. This alteration results from a G to C substitution at nucleotide position 26, causing the glycine (G) at amino acid position 9 to be replaced by an alanine (A). 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

0.083

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0017

T;T;T;T;T;T;T;T;.;.;T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.67

.;T;.;.;.;.;.;.;T;T;T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.075

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.75

N;N;N;N;N;N;N;N;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.060

.;N;N;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.031

Sift

Benign

0.51

.;T;T;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.77

T;T;T;T;T;T;T;T;.;.;T;T

Polyphen

0.0040

B;B;B;B;B;B;B;B;.;.;.;.

Vest4

0.10

MutPred

0.18

Loss of disorder (P = 0.0961);Loss of disorder (P = 0.0961);Loss of disorder (P = 0.0961);Loss of disorder (P = 0.0961);Loss of disorder (P = 0.0961);Loss of disorder (P = 0.0961);Loss of disorder (P = 0.0961);Loss of disorder (P = 0.0961);Loss of disorder (P = 0.0961);Loss of disorder (P = 0.0961);Loss of disorder (P = 0.0961);Loss of disorder (P = 0.0961);

MVP

0.11

MPC

0.23

ClinPred

0.089

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.051

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over