chr16-75540132-C-T

Variant names:

• chr16-75540132-C-T
• rs2242406
• NM_001077418.3:c.813G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001077418.3(TMEM231):​c.813G>A​(p.Val271Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 1,613,238 control chromosomes in the GnomAD database, including 23,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (2475 hom., cov: 33)
  • Exomes 𝑓: 0.097 (21116 hom.)
• Consequence: TMEM231 NM_001077418.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.923

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]

ENSG00000260092 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 16-75540132-C-T is Benign according to our data. Variant chr16-75540132-C-T is described in ClinVar as [Benign]. Clinvar id is 130591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.923 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3	c.813G>A	p.Val271Val	synonymous_variant	Exon 7 of 7	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077416.2	c.972G>A	p.Val324Val	synonymous_variant	Exon 6 of 6		NP_001070884.2
TMEM231	NR_074083.2	n.979G>A		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM231	ENST00000258173.11	c.813G>A	p.Val271Val	synonymous_variant	Exon 7 of 7	1	NM_001077418.3	ENSP00000258173.5
TMEM231	ENST00000568377.5	c.900G>A	p.Val300Val	synonymous_variant	Exon 6 of 6	1		ENSP00000476267.1
TMEM231	ENST00000565067.5	c.669G>A	p.Val223Val	synonymous_variant	Exon 6 of 6	5		ENSP00000457254.1
TMEM231	ENST00000562410.5	n.*615G>A		non_coding_transcript_exon_variant	Exon 7 of 7	1		ENSP00000454582.1
TMEM231	ENST00000570006.5	n.*193G>A		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000455520.1
TMEM231	ENST00000562410.5	n.*615G>A		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000454582.1
TMEM231	ENST00000570006.5	n.*193G>A		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000455520.1
ENSG00000260092	ENST00000460606.1	n.157+2470G>A		intron_variant	Intron 2 of 4	1		ENSP00000457544.1

Frequencies

GnomAD3 genomes AF: 0.0995 AC: 15129 AN: 152106 Hom.: 2468 Cov.: 33

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.109

GnomAD2 exomes AF: 0.184 AC: 45706 AN: 247938 AF XY: 0.177

Gnomad AFR exome AF: 0.0189

Gnomad AMR exome AF: 0.422

Gnomad ASJ exome AF: 0.0868

Gnomad EAS exome AF: 0.754

Gnomad FIN exome AF: 0.0670

Gnomad NFE exome AF: 0.0524

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.0969 AC: 141614 AN: 1461012 Hom.: 21116 Cov.: 32 AF XY: 0.101 AC XY: 73122 AN XY: 726822

Gnomad4 AFR exome AF: 0.0141 AC: 473 AN: 33476

Gnomad4 AMR exome AF: 0.406 AC: 18102 AN: 44550

Gnomad4 ASJ exome AF: 0.0862 AC: 2253 AN: 26122

Gnomad4 EAS exome AF: 0.742 AC: 29430 AN: 39668

Gnomad4 SAS exome AF: 0.272 AC: 23455 AN: 86130

Gnomad4 FIN exome AF: 0.0661 AC: 3525 AN: 53352

Gnomad4 NFE exome AF: 0.0511 AC: 56817 AN: 1111610

Gnomad4 Remaining exome AF: 0.117 AC: 7054 AN: 60340

GnomAD4 genome AF: 0.0995 AC: 15143 AN: 152226 Hom.: 2475 Cov.: 33 AF XY: 0.112 AC XY: 8331 AN XY: 74402

Gnomad4 AFR AF: 0.0192 AC: 0.0191975 AN: 0.0191975

Gnomad4 AMR AF: 0.284 AC: 0.284235 AN: 0.284235

Gnomad4 ASJ AF: 0.101 AC: 0.101094 AN: 0.101094

Gnomad4 EAS AF: 0.720 AC: 0.71955 AN: 0.71955

Gnomad4 SAS AF: 0.307 AC: 0.306894 AN: 0.306894

Gnomad4 FIN AF: 0.0674 AC: 0.0673639 AN: 0.0673639

Gnomad4 NFE AF: 0.0500 AC: 0.0500441 AN: 0.0500441

Gnomad4 OTH AF: 0.110 AC: 0.110218 AN: 0.110218

Alfa AF: 0.0591 Hom.: 388

Bravo AF: 0.116

Asia WGS AF: 0.446 AC: 1546 AN: 3478

EpiCase AF: 0.0541

EpiControl AF: 0.0552

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

May 28, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joubert syndrome 20;C3809352:Meckel syndrome, type 11 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	2.4
DANN	Benign	0.82
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2242406; hg19: chr16-75574030; COSMIC: COSV50739084; COSMIC: COSV50739084;