Genetic Variant NM_001130924.3:c.694G>T (chr1-9601192-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130924.3(TMEM201):c.694G>T(p.Ala232Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A232V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TMEM201
NM_001130924.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.282

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17215377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM201	NM_001130924.3 link	c.694G>T	p.Ala232Ser	missense_variant	Exon 5 of 11	ENST00000340381.11	NP_001124396.2	Q5SNT2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM201	ENST00000340381.11 link	c.694G>T	p.Ala232Ser	missense_variant	Exon 5 of 11	5	NM_001130924.3	ENSP00000344503.6	Q5SNT2-1
TMEM201	ENST00000416541.5 link	c.421G>T	p.Ala141Ser	missense_variant	Exon 3 of 8	1		ENSP00000393626.1	H0Y4R5
TMEM201	ENST00000340305.9 link	c.694G>T	p.Ala232Ser	missense_variant	Exon 5 of 6	1		ENSP00000344772.5	Q5SNT2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000800

AC:

AN:

250062

AF XY:

0.00000739

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460570

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111722

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.21

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

0.28

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.047

Sift

Benign

0.17

T;T

Sift4G

Benign

0.089

T;T

Polyphen

0.13

B;.

Vest4

0.15

MutPred

0.47

Gain of glycosylation at A232 (P = 0.0144);Gain of glycosylation at A232 (P = 0.0144);

MVP

0.18

MPC

0.59

ClinPred

0.097

GERP RS

-0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.028

gMVP

0.53

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over