Variant 1-165743268-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_019026.6(TMCO1):c.367T>C(p.Ser123Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TMCO1
NM_019026.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

TMCO1 (HGNC:18188): (transmembrane and coiled-coil domains 1) This locus encodes a transmembrane protein. Mutations at this locus have been associated with craniofacial dysmorphism, skeletal anomalies, and cognitive disability. Mutations at this locus have also been associated with open angle glaucoma blindness. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]

TMCO1 links:

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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
TMCO1	NM_019026.6 link	c.367T>C	p.Ser123Pro	missense_variant	Exon 6 of 7	ENST00000367881.11	NP_061899.3	Q9UM00-1
TMCO1	NM_001256164.1 link	c.418T>C	p.Ser140Pro	missense_variant	Exon 6 of 7		NP_001243093.1	B7Z591
TMCO1	NM_001256165.1 link	c.331T>C	p.Ser111Pro	missense_variant	Exon 6 of 7		NP_001243094.1	B7Z591
TMCO1	NR_045818.1 link	n.461T>C		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO1	ENST00000367881.11 link	c.367T>C	p.Ser123Pro	missense_variant	Exon 6 of 7	1	NM_019026.6	ENSP00000356856.6		Q9UM00-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727186

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.367T>C (p.S123P) alteration is located in exon 6 (coding exon 6) of the TMCO1 gene. This alteration results from a T to C substitution at nucleotide position 367, causing the serine (S) at amino acid position 123 to be replaced by a proline (P). 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

0.27

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

.;T;.;.;.;.

Eigen

Benign

-0.084

Eigen_PC

Benign

0.087

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

D;D;.;.;T;D

M_CAP

Benign

0.0041

MetaRNN

Uncertain

0.52

D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L;.;.;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-4.5

.;D;.;.;.;.

REVEL

Benign

0.24

Sift

Uncertain

0.0030

.;D;.;.;.;.

Sift4G

Benign

0.24

T;T;T;T;T;.

Polyphen

0.051

.;B;.;.;.;.

Vest4

0.81

MutPred

0.50

.;Gain of loop (P = 0.024);.;.;.;.;

MVP

0.15

MPC

0.79

ClinPred

0.97

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.96

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

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