16-75556194-G-C

Position:

chr16-75556194-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001077418.3(TMEM231):c.16C>G(p.Leu6Val) variant causes a missense change. The variant allele was found at a frequency of 0.0938 in 1,485,022 control chromosomes in the GnomAD database, including 19,435 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2663 hom., cov: 33)

Exomes 𝑓: 0.091 ( 16772 hom. )

Consequence

TMEM231
NM_001077418.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.96

Variant links:

Genes affected

TMEM231 (HGNC:37234): (transmembrane protein 231) This gene encodes a transmembrane protein, which is a component of the B9 complex involved in the formation of the diffusion barrier between the cilia and plasma membrane. Mutations in this gene cause Joubert syndrome (JBTS). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

TMEM231 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8012524E-5).

BP6

Variant 16-75556194-G-C is Benign according to our data. Variant chr16-75556194-G-C is described in ClinVar as [Benign]. Clinvar id is 130587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM231	NM_001077418.3 linkuse as main transcript	c.16C>G	p.Leu6Val	missense_variant	1/7	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077416.2 linkuse as main transcript	c.78C>G	p.Ser26Arg	missense_variant	1/6		NP_001070884.2
TMEM231	NR_074083.2 linkuse as main transcript	n.59C>G		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM231	ENST00000258173.11 linkuse as main transcript	c.16C>G	p.Leu6Val	missense_variant	1/7	1	NM_001077418.3	ENSP00000258173	P1	Q9H6L2-1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18175

AN:

152146

Hom.:

2652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0929

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.709

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.0581

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0477

Gnomad OTH

AF:

0.126

GnomAD3 exomes

AF:

0.210

AC:

24008

AN:

114184

Hom.:

5411

AF XY:

0.196

AC XY:

12479

AN XY:

63530

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.438

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.751

Gnomad SAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.0584

Gnomad NFE exome

AF:

0.0520

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.0908

AC:

121014

AN:

1332758

Hom.:

16772

Cov.:

AF XY:

0.0945

AC XY:

61597

AN XY:

651754

show subpopulations

Gnomad4 AFR exome

AF:

0.0918

Gnomad4 AMR exome

AF:

0.399

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.719

Gnomad4 SAS exome

AF:

0.274

Gnomad4 FIN exome

AF:

0.0551

Gnomad4 NFE exome

AF:

0.0486

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.120

AC:

18216

AN:

152264

Hom.:

2663

Cov.:

AF XY:

0.132

AC XY:

9802

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0934

Gnomad4 AMR

AF:

0.293

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.710

Gnomad4 SAS

AF:

0.304

Gnomad4 FIN

AF:

0.0581

Gnomad4 NFE

AF:

0.0477

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.0786

Hom.:

1200

Bravo

AF:

0.140

TwinsUK

AF:

0.0464

AC:

172

ALSPAC

AF:

0.0467

AC:

180

ESP6500AA

AF:

0.0835

AC:

301

ESP6500EA

AF:

0.0463

AC:

361

ExAC

AF:

0.156

AC:

17902

Asia WGS

AF:

0.449

AC:

1557

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 02, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Joubert syndrome 20;C3809352:Meckel syndrome, type 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Joubert syndrome 20

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.060

T;T

Eigen

Benign

-0.038

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.000018

T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

0.50

P;P;P

PROVEAN

Benign

0.86

N;N

REVEL

Benign

0.099

Sift

Benign

1.0

T;T

Sift4G

Benign

0.78

T;T

Polyphen

0.021

B;.

Vest4

0.045

ClinPred

0.075

GERP RS

4.6

Varity_R

0.11

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

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