chr16-75539856-G-A

Variant names:

• chr16-75539856-G-A
• rs2242408
• ENST00000258173:c.*138C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001077418.3(TMEM231):​c.*138C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 689,014 control chromosomes in the GnomAD database, including 2,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (560 hom., cov: 32)
  • Exomes 𝑓: 0.067 (1525 hom.)
• Consequence: TMEM231 NM_001077418.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.584

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-75539856-G-A is Benign according to our data. Variant chr16-75539856-G-A is described in ClinVar as [Benign]. Clinvar id is 1296183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3	c.*138C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077416.2	c.*138C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001070884.2
TMEM231	NR_074083.2	n.1255C>T		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.*138C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_001077418.3	ENSP00000258173.5
TMEM231	ENST00000568377	c.*138C>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000476267.1
TMEM231	ENST00000565067	c.*138C>T		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000457254.1
TMEM231	ENST00000562410.5	n.*891C>T		non_coding_transcript_exon_variant	Exon 7 of 7	1		ENSP00000454582.1
TMEM231	ENST00000562410.5	n.*891C>T		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000454582.1
ENSG00000260092	ENST00000460606.1	n.157+2746C>T		intron_variant	Intron 2 of 4	1		ENSP00000457544.1
TMEM231	ENST00000570006.5	n.*469C>T		downstream_gene_variant		5		ENSP00000455520.1

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 12163 AN: 151864 Hom.: 558 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0412

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.0671

GnomAD4 exome AF: 0.0675 AC: 36249 AN: 537034 Hom.: 1525 Cov.: 7 AF XY: 0.0695 AC XY: 19228 AN XY: 276818

Gnomad4 AFR exome AF: 0.129 AC: 1790 AN: 13888

Gnomad4 AMR exome AF: 0.0379 AC: 610 AN: 16094

Gnomad4 ASJ exome AF: 0.0791 AC: 1075 AN: 13590

Gnomad4 EAS exome AF: 0.0293 AC: 877 AN: 29924

Gnomad4 SAS exome AF: 0.115 AC: 4547 AN: 39502

Gnomad4 FIN exome AF: 0.0911 AC: 3308 AN: 36306

Gnomad4 NFE exome AF: 0.0609 AC: 21775 AN: 357308

Gnomad4 Remaining exome AF: 0.0741 AC: 2100 AN: 28336

GnomAD4 genome AF: 0.0801 AC: 12167 AN: 151980 Hom.: 560 Cov.: 32 AF XY: 0.0802 AC XY: 5953 AN XY: 74270

Gnomad4 AFR AF: 0.120 AC: 0.119986 AN: 0.119986

Gnomad4 AMR AF: 0.0410 AC: 0.0409675 AN: 0.0409675

Gnomad4 ASJ AF: 0.0781 AC: 0.078098 AN: 0.078098

Gnomad4 EAS AF: 0.0317 AC: 0.031746 AN: 0.031746

Gnomad4 SAS AF: 0.119 AC: 0.118869 AN: 0.118869

Gnomad4 FIN AF: 0.0895 AC: 0.0895056 AN: 0.0895056

Gnomad4 NFE AF: 0.0646 AC: 0.0646424 AN: 0.0646424

Gnomad4 OTH AF: 0.0664 AC: 0.0664137 AN: 0.0664137

Alfa AF: 0.0784 Hom.: 65

Bravo AF: 0.0781

Asia WGS AF: 0.101 AC: 350 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.51
Mutation Taster		=100/0	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: rs2242408; hg19: chr16-75573754;