Variant 1-9596940-G-A 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_001130924.3(TMEM201):c.316G>A(p.Asp106Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,612,768 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: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

TMEM201
NM_001130924.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

Variant links:

Genes affected

TMEM201 (HGNC:33719): (transmembrane protein 201) Predicted to enable actin filament binding activity and lamin binding activity. Involved in centrosome localization; nuclear envelope organization; and protein localization to nuclear envelope. Located in nuclear envelope. Is integral component of nuclear inner membrane. Colocalizes with cortical endoplasmic reticulum and spindle pole centrosome. [provided by Alliance of Genome Resources, Apr 2022]

TMEM201 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=0.0702039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM201	NM_001130924.3 linkuse as main transcript	c.316G>A	p.Asp106Asn	missense_variant	3/11	ENST00000340381.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM201	ENST00000340381.11 linkuse as main transcript	c.316G>A	p.Asp106Asn	missense_variant	3/11	5	NM_001130924.3	P1	Q5SNT2-1
TMEM201	ENST00000416541.5 linkuse as main transcript	c.46G>A	p.Asp16Asn	missense_variant	1/8	1
TMEM201	ENST00000340305.9 linkuse as main transcript	c.316G>A	p.Asp106Asn	missense_variant	3/6	1			Q5SNT2-2

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.0000360

AC:

AN:

249796

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135440

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1460544

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000177

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00382

Alfa

AF:

0.000155

Hom.:

Bravo

AF:

0.000310

ExAC

AF:

0.0000412

AC:

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

Feb 02, 2024

The c.316G>A (p.D106N) alteration is located in exon 3 (coding exon 3) of the TMEM201 gene. This alteration results from a G to A substitution at nucleotide position 316, causing the aspartic acid (D) at amino acid position 106 to be replaced by an asparagine (N). 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

0.096

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.46

N;N

MutationTaster

Benign

0.74

D;D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.027

Sift

Benign

0.29

T;T

Sift4G

Benign

0.092

T;T

Polyphen

0.0090

B;.

Vest4

0.19

MutPred

0.33

Gain of glycosylation at P107 (P = 0.1369);Gain of glycosylation at P107 (P = 0.1369);

MVP

0.093

MPC

0.41

ClinPred

0.13

GERP RS

3.3

Varity_R

0.049

gMVP

0.37

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

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