rs1415483600

Variant names:

• chr16-75545825-C-A
• NM_001077418.3:c.438+1G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-75545825-C-A
• chr16-75545825-C-G
• chr16-75545825-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Strong

The NM_001077418.3(TMEM231):​c.438+1G>T variant causes a splice donor, intron change. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 13)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: TMEM231 NM_001077418.3 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.11

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 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.13564669 fraction of the gene. Cryptic splice site detected, with MaxEntScore 4.5, offset of -38, new splice context is: tcgGTgtgc. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3	c.438+1G>T		splice_donor_variant, intron_variant	Intron 3 of 6	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077416.2	c.597+1G>T		splice_donor_variant, intron_variant	Intron 2 of 5		NP_001070884.2
TMEM231	NR_074083.2	n.604+1G>T		splice_donor_variant, intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM231	ENST00000258173.11	c.438+1G>T		splice_donor_variant, intron_variant	Intron 3 of 6	1	NM_001077418.3	ENSP00000258173.5
TMEM231	ENST00000568377.5	c.525+1G>T		splice_donor_variant, intron_variant	Intron 2 of 5	1		ENSP00000476267.1
TMEM231	ENST00000565067.5	c.438+1G>T		splice_donor_variant, intron_variant	Intron 3 of 5	5		ENSP00000457254.1
TMEM231	ENST00000562410.5	n.*240+1G>T		splice_donor_variant, intron_variant	Intron 3 of 6	1		ENSP00000454582.1
TMEM231	ENST00000570006.5	n.400+39G>T		intron_variant	Intron 3 of 6	5		ENSP00000455520.1

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD4 exome AF: 0.00000186 AC: 2 AN: 1076866 Hom.: 0 Cov.: 15 AF XY: 0.00000187 AC XY: 1 AN XY: 535394

Gnomad4 AFR exome AF: 0.00

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: 0.00000123

Gnomad4 OTH exome AF: 0.0000214

GnomAD4 genome Cov.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
GERP RS		3.8

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.93
SpliceAI score (max)		0.97		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.97		Position offset: 1

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: chr16-75579723;