dbSNP rs780494581: TMEM231:p.Glu313Asp (chr16-75540006-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077418.3(TMEM231):c.939G>C(p.Glu313Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM231
NM_001077418.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

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:

ENSG00000260092 (HGNC:):

ENSG00000260092 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=0.12213865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3 link	c.939G>C	p.Glu313Asp	missense_variant	Exon 7 of 7	ENST00000258173.11	NP_001070886.1	Q9H6L2-1
TMEM231	NM_001077416.2 link	c.1098G>C	p.Glu366Asp	missense_variant	Exon 6 of 6		NP_001070884.2	Q9H6L2
TMEM231	NR_074083.2 link	n.1105G>C		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM231	ENST00000258173.11 link	c.939G>C	p.Glu313Asp	missense_variant	Exon 7 of 7	1	NM_001077418.3	ENSP00000258173.5	Q9H6L2-1
TMEM231	ENST00000568377.5 link	c.1026G>C	p.Glu342Asp	missense_variant	Exon 6 of 6	1		ENSP00000476267.1	Q9H6L2-2
TMEM231	ENST00000565067.5 link	c.795G>C	p.Glu265Asp	missense_variant	Exon 6 of 6	5		ENSP00000457254.1	H3BTN6
TMEM231	ENST00000562410.5 link	n.*741G>C		non_coding_transcript_exon_variant	Exon 7 of 7	1		ENSP00000454582.1	H3BMW7
TMEM231	ENST00000562410.5 link	n.*741G>C		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000454582.1	H3BMW7
ENSG00000260092	ENST00000460606.1 link	n.157+2596G>C		intron_variant	Intron 2 of 4	1		ENSP00000457544.1	H3BUA1
TMEM231	ENST00000570006.5 link	n.*319G>C		downstream_gene_variant		5		ENSP00000455520.1	H3BPY4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.86e-7

AC:

AN:

1458658

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725588

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

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0016

T;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.054

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.3

M;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

N;.;N

REVEL

Benign

0.13

Sift

Benign

0.036

D;.;T

Sift4G

Benign

0.10

T;T;T

Polyphen

0.12

B;.;.

Vest4

0.087

MutPred

0.15

Loss of stability (P = 0.0852);.;.;

MVP

0.18

MPC

0.028

ClinPred

0.82

GERP RS

2.9

Varity_R

0.066

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over