rs200063331

Variant names:

• chr16-75556024-G-A
• ENST00000568377.5:c.176C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-75556024-G-A
• chr16-75556024-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077416.2(TMEM231):​c.248C>T​(p.Ser83Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,417,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TMEM231 NM_001077416.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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]

ENSG00000259992 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080993235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3	c.139+47C>T		intron_variant	Intron 1 of 6	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077416.2	c.248C>T	p.Ser83Leu	missense_variant	Exon 1 of 6		NP_001070884.2
TMEM231	NR_074083.2	n.182+47C>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM231	ENST00000568377.5	c.176C>T	p.Ser59Leu	missense_variant	Exon 1 of 6	1		ENSP00000476267.1
TMEM231	ENST00000258173.11	c.139+47C>T		intron_variant	Intron 1 of 6	1	NM_001077418.3	ENSP00000258173.5
TMEM231	ENST00000565067.5	c.139+47C>T		intron_variant	Intron 1 of 5	5		ENSP00000457254.1
TMEM231	ENST00000562410.5	n.139+47C>T		intron_variant	Intron 1 of 6	1		ENSP00000454582.1
TMEM231	ENST00000570006.5	n.139+47C>T		intron_variant	Intron 1 of 6	5		ENSP00000455520.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000282 AC: 4 AN: 1417486 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 700782

Gnomad4 AFR exome AF: 0.0000310

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000275

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Uncertain	0.99
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.89	T
PrimateAI	Uncertain	0.53	T
Sift4G	Benign	0.13	T
Vest4		0.092
MVP		0.055
MPC		0.78
ClinPred		0.48	T
GERP RS		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-75589922;