Variant chr15-76169817-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000388942.9(TMEM266):c.434C>G(p.Thr145Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMEM266
ENST00000388942.9 missense, splice_region

Scores

Splicing: ADA: 0.1102

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04

Variant links:

Genes affected

TMEM266 (HGNC:26763): (transmembrane protein 266) Enables protein homodimerization activity. Predicted to be involved in transmembrane transport. Located in cytosol; dendrite; and plasma membrane. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM266 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMEM266	NM_152335.5 linkuse as main transcript	c.434C>G	p.Thr145Ser	missense_variant, splice_region_variant	6/11	ENST00000388942.9
TMEM266	XM_047432151.1 linkuse as main transcript	c.458C>G	p.Thr153Ser	missense_variant, splice_region_variant	8/13
TMEM266	XM_017021915.2 linkuse as main transcript	c.458C>G	p.Thr153Ser	missense_variant, splice_region_variant	8/13
TMEM266	XM_005254160.4 linkuse as main transcript	c.-95C>G		splice_region_variant, 5_prime_UTR_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM266	ENST00000388942.9 linkuse as main transcript	c.434C>G	p.Thr145Ser	missense_variant, splice_region_variant	6/11	5	NM_152335.5	P1	Q2M3C6-1
TMEM266	ENST00000561302.6 linkuse as main transcript	c.279C>G	p.Asp93Glu	missense_variant, splice_region_variant, NMD_transcript_variant	5/11	1
TMEM266	ENST00000484722.6 linkuse as main transcript	c.*46C>G		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	6/11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727084

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

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

Oct 13, 2023

The c.458C>G (p.T153S) alteration is located in exon 6 (coding exon 5) of the TMEM266 gene. This alteration results from a C to G substitution at nucleotide position 458, causing the threonine (T) at amino acid position 153 to be replaced by a serine (S). 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

Pathogenic

0.70

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.057

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.84

MetaSVM

Pathogenic

1.1

MutationTaster

Benign

1.0

PROVEAN

Benign

-2.0

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.81

MutPred

0.46

Gain of relative solvent accessibility (P = 0.0507);

MVP

0.96

MPC

0.75

ClinPred

0.89

GERP RS

5.1

Varity_R

0.28

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.11

dbscSNV1_RF

Benign

0.36

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

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