rs2550889

Positions:

• chr16-75538700-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001077418.3(TMEM231):​c.*1294C>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 0.0354 in 152,228 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.035 (151 hom., cov: 33)
  • Exomes 𝑓: 0.056 (0 hom.)
• Consequence: TMEM231 NM_001077418.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM231	NM_001077418.3	c.*1294C>T		3_prime_UTR_variant	7/7	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077416.2	c.*1294C>T		3_prime_UTR_variant	6/6		NP_001070884.2
TMEM231	NR_074083.2	n.2411C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM231	ENST00000258173.11	c.*1294C>T		3_prime_UTR_variant	7/7	1	NM_001077418.3	ENSP00000258173	P1

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5389 AN: 152092 Hom.: 150 Cov.: 33

Gnomad AFR AF: 0.0775

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.00594

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0321

GnomAD4 exome AF: 0.0556 AC: 1 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0354 AC: 5390 AN: 152210 Hom.: 151 Cov.: 33 AF XY: 0.0352 AC XY: 2623 AN XY: 74418

Gnomad4 AFR AF: 0.0774

Gnomad4 AMR AF: 0.0196

Gnomad4 ASJ AF: 0.0328

Gnomad4 EAS AF: 0.0290

Gnomad4 SAS AF: 0.0614

Gnomad4 FIN AF: 0.00594

Gnomad4 NFE AF: 0.0167

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0273 Hom.: 18

Bravo AF: 0.0379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.58

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: rs2550889; hg19: chr16-75572598;