dbSNP rs761776268: TMEM205:p.Met13Ile (chr19-11345581-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198536.3(TMEM205):c.39G>T(p.Met13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

TMEM205
NM_198536.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM205	NM_198536.3 link	c.39G>T	p.Met13Ile	missense_variant	Exon 1 of 3	ENST00000354882.10	NP_940938.1	Q6UW68A0A024R7D3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM205	ENST00000354882.10 link	c.39G>T	p.Met13Ile	missense_variant	Exon 1 of 3	1	NM_198536.3	ENSP00000346954.4		Q6UW68

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251366

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135880

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727234

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:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0032

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

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.61

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

M_CAP

Benign

0.0029

MetaRNN

Benign

0.098

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

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

PrimateAI

Benign

0.33

PROVEAN

Benign

0.32

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

REVEL

Benign

0.022

Sift

Benign

0.30

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

Sift4G

Benign

0.66

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

Polyphen

0.0

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

Vest4

0.16

MutPred

0.38

Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);

MVP

0.38

MPC

0.24

ClinPred

0.33

GERP RS

4.1

Varity_R

0.11

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: -23

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over