chr16-75539986-T-C

Variant names:

• chr16-75539986-T-C
• rs2242407
• NM_001077418.3:c.*8A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001077418.3(TMEM231):​c.*8A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,599,648 control chromosomes in the GnomAD database, including 52,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4830 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47357 hom.)
• Consequence: TMEM231 NM_001077418.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.467

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 16-75539986-T-C is Benign according to our data. Variant chr16-75539986-T-C is described in ClinVar as [Benign]. Clinvar id is 257328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-75539986-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3	c.*8A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077416.2	c.*8A>G		3_prime_UTR_variant	Exon 6 of 6		NP_001070884.2
TMEM231	NR_074083.2	n.1125A>G		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM231	ENST00000258173	c.*8A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001077418.3	ENSP00000258173.5
TMEM231	ENST00000568377	c.*8A>G		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000476267.1
TMEM231	ENST00000565067	c.*8A>G		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000457254.1
TMEM231	ENST00000562410.5	n.*761A>G		non_coding_transcript_exon_variant	Exon 7 of 7	1		ENSP00000454582.1
TMEM231	ENST00000562410.5	n.*761A>G		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000454582.1
ENSG00000260092	ENST00000460606.1	n.157+2616A>G		intron_variant	Intron 2 of 4	1		ENSP00000457544.1
TMEM231	ENST00000570006.5	n.*339A>G		downstream_gene_variant		5		ENSP00000455520.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 37791 AN: 149860 Hom.: 4826 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.230

GnomAD3 exomes AF: 0.234 AC: 56179 AN: 240376 Hom.: 7030 AF XY: 0.237 AC XY: 30826 AN XY: 130168

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.201

Gnomad SAS exome AF: 0.229

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.252 AC: 365984 AN: 1449680 Hom.: 47357 Cov.: 31 AF XY: 0.252 AC XY: 181851 AN XY: 720562

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.252 AC: 37817 AN: 149968 Hom.: 4830 Cov.: 32 AF XY: 0.251 AC XY: 18380 AN XY: 73354

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.233

Alfa AF: 0.249 Hom.: 2145

Asia WGS AF: 0.284 AC: 983 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jan 22, 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. -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

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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	-0.96
CADD	Benign	0.068
DANN	Benign	0.33

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: rs2242407; hg19: chr16-75573884; COSMIC: COSV50737805; COSMIC: COSV50737805;