16-75539856-G-A

Position:

• chr16-75539856-G-A

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.*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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TMEM231	NM_001077418.3	c.*138C>T		3_prime_UTR_variant	7/7	ENST00000258173.11
TMEM231	NM_001077416.2	c.*138C>T		3_prime_UTR_variant	6/6
TMEM231	NR_074083.2	n.1255C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM231	ENST00000258173.11	c.*138C>T		3_prime_UTR_variant	7/7	1	NM_001077418.3	P1

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

Gnomad4 AMR exome AF: 0.0379

Gnomad4 ASJ exome AF: 0.0791

Gnomad4 EAS exome AF: 0.0293

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.0911

Gnomad4 NFE exome AF: 0.0609

Gnomad4 OTH exome AF: 0.0741

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

Gnomad4 AMR AF: 0.0410

Gnomad4 ASJ AF: 0.0781

Gnomad4 EAS AF: 0.0317

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.0646

Gnomad4 OTH AF: 0.0664

Alfa AF: 0.0769 Hom.: 61

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.51

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;