16-75539855-C-T

Position:

• chr16-75539855-C-T

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.*139G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 674,670 control chromosomes in the GnomAD database, including 9,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2208 hom., cov: 31)
  • Exomes 𝑓: 0.16 (7579 hom.)
• Consequence: TMEM231 NM_001077418.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.41

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=-0.96).
• BP6: Variant 16-75539855-C-T is Benign according to our data. Variant chr16-75539855-C-T is described in ClinVar as [Benign]. Clinvar id is 1247731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM231	NM_001077418.3	c.*139G>A		3_prime_UTR_variant	7/7	ENST00000258173.11
TMEM231	NM_001077416.2	c.*139G>A		3_prime_UTR_variant	6/6
TMEM231	NR_074083.2	n.1256G>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM231	ENST00000258173.11	c.*139G>A		3_prime_UTR_variant	7/7	1	NM_001077418.3	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 24967 AN: 150856 Hom.: 2206 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.161 AC: 84255 AN: 523698 Hom.: 7579 Cov.: 7 AF XY: 0.160 AC XY: 43101 AN XY: 269982

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.0942

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.165 AC: 24977 AN: 150972 Hom.: 2208 Cov.: 31 AF XY: 0.164 AC XY: 12076 AN XY: 73676

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.158

Alfa AF: 0.185 Hom.: 281

Bravo AF: 0.157

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 14, 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	-0.96
CADD	Benign	1.4
DANN	Benign	0.39

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: rs459211; hg19: chr16-75573753;