16-75556215-C-T

Variant names:

• chr16-75556215-C-T
• rs3743602
• NM_001077418.3:c.-6G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077418.3(TMEM231):​c.-6G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000237 in 1,264,516 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: TMEM231 NM_001077418.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3	c.-6G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077418.3	c.-6G>A		5_prime_UTR_variant	Exon 1 of 7	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077416.2	c.57G>A	p.Arg19Arg	synonymous_variant	Exon 1 of 6		NP_001070884.2
TMEM231	NR_074083.2	n.38G>A		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM231	ENST00000258173.11	c.-6G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	NM_001077418.3	ENSP00000258173.5
TMEM231	ENST00000568377.5	c.-16G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	1		ENSP00000476267.1
TMEM231	ENST00000565067.5	c.-6G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	5		ENSP00000457254.1
TMEM231	ENST00000258173.11	c.-6G>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_001077418.3	ENSP00000258173.5
TMEM231	ENST00000568377.5	c.-16G>A		5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000476267.1
TMEM231	ENST00000565067.5	c.-6G>A		5_prime_UTR_variant	Exon 1 of 6	5		ENSP00000457254.1
TMEM231	ENST00000562410.5	n.-6G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1		ENSP00000454582.1
TMEM231	ENST00000570006.5	n.-6G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	5		ENSP00000455520.1
TMEM231	ENST00000562410.5	n.-6G>A		non_coding_transcript_exon_variant	Exon 1 of 7	1		ENSP00000454582.1
TMEM231	ENST00000570006.5	n.-6G>A		non_coding_transcript_exon_variant	Exon 1 of 7	5		ENSP00000455520.1
TMEM231	ENST00000562410.5	n.-6G>A		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000454582.1
TMEM231	ENST00000570006.5	n.-6G>A		5_prime_UTR_variant	Exon 1 of 7	5		ENSP00000455520.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000183 AC: 1 AN: 54578 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 30658

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000316

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000237 AC: 3 AN: 1264516 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 613856

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000571

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: 0.00000195

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_noAF	Benign	-0.68
CADD	Benign	7.4
DANN	Benign	0.93

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: rs3743602; hg19: chr16-75590113;