rs2550889

Variant names:

• chr16-75538700-G-A
• rs2550889
• ENST00000562410.5:n.*2047C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000562410.5(TMEM231):​n.*2047C>T variant causes a non coding transcript exon 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 ENST00000562410.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 3 publications found

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]

TMEM231 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Joubert syndrome 20

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• orofaciodigital syndrome III

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000260092 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3	c.*1294C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000258173.11	NP_001070886.1
TMEM231	NR_074083.2	n.2411C>T		non_coding_transcript_exon_variant	Exon 7 of 7
TMEM231	NM_001077416.2	c.*1294C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001070884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM231	ENST00000562410.5	n.*2047C>T		non_coding_transcript_exon_variant	Exon 7 of 7	1		ENSP00000454582.1
TMEM231	ENST00000258173.11	c.*1294C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_001077418.3	ENSP00000258173.5
TMEM231	ENST00000568377.5	c.*1294C>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000476267.1
TMEM231	ENST00000562410.5	n.*2047C>T		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000454582.1
ENSG00000260092	ENST00000460606.1	n.157+3902C>T		intron_variant	Intron 2 of 4	1		ENSP00000457544.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.0774 AC: 3214 AN: 41518

American (AMR) AF: 0.0196 AC: 300 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 114 AN: 3472

East Asian (EAS) AF: 0.0290 AC: 150 AN: 5172

South Asian (SAS) AF: 0.0614 AC: 296 AN: 4820

European-Finnish (FIN) AF: 0.00594 AC: 63 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0167 AC: 1133 AN: 68008

Other (OTH) AF: 0.0317 AC: 67 AN: 2112

Alfa AF: 0.0292 Hom.: 20

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
PhyloP100		-0.12
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

Other links and lift over

dbSNP: rs2550889; hg19: chr16-75572598;