chr19-11345581-C-T

Position:

• chr19-11345581-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198536.3(TMEM205):​c.39G>A​(p.Met13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMEM205 NM_198536.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00

Genes affected

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

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

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]

ACMG classification

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=0.12995708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM205	NM_198536.3	c.39G>A	p.Met13Ile	missense_variant	1/3	ENST00000354882.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM205	ENST00000354882.10	c.39G>A	p.Met13Ile	missense_variant	1/3	1	NM_198536.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Uncertain	0.98
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	0.87	D
LIST_S2	Benign	0.61	.;T;.;.;.;.;.;.;T;T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.13	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;N;N;N;N;N;N;N;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.32	.;N;N;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.094
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		0.57	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.11
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs761776268; hg19: chr19-11456257;