rs746970206

Variant names:

• chr16-75540025-C-A
• NM_001077418.3:c.920G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-75540025-C-A
• chr16-75540025-C-G
• chr16-75540025-C-T

Variant summary

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

The NM_001077418.3(TMEM231):​c.920G>T​(p.Arg307Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM231 NM_001077418.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.891

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]

ENSG00000260092 (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 (MetaRNN=0.064769536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3	c.920G>T	p.Arg307Leu	missense_variant	Exon 7 of 7	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077416.2	c.1079G>T	p.Arg360Leu	missense_variant	Exon 6 of 6		NP_001070884.2
TMEM231	NR_074083.2	n.1086G>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM231	ENST00000258173.11	c.920G>T	p.Arg307Leu	missense_variant	Exon 7 of 7	1	NM_001077418.3	ENSP00000258173.5
TMEM231	ENST00000568377.5	c.1007G>T	p.Arg336Leu	missense_variant	Exon 6 of 6	1		ENSP00000476267.1
TMEM231	ENST00000565067.5	c.776G>T	p.Arg259Leu	missense_variant	Exon 6 of 6	5		ENSP00000457254.1
TMEM231	ENST00000562410.5	n.*722G>T		non_coding_transcript_exon_variant	Exon 7 of 7	1		ENSP00000454582.1
TMEM231	ENST00000570006.5	n.*300G>T		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000455520.1
TMEM231	ENST00000562410.5	n.*722G>T		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000454582.1
TMEM231	ENST00000570006.5	n.*300G>T		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000455520.1
ENSG00000260092	ENST00000460606.1	n.157+2577G>T		intron_variant	Intron 2 of 4	1		ENSP00000457544.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460792 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726666

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.060
DANN	Benign	0.71
DEOGEN2	Benign	0.0010	T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.065	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.90	N;.;.
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.60	N;.;N
REVEL	Benign	0.076
Sift	Benign	0.20	T;.;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.011	B;.;.
Vest4		0.13
MutPred		0.54		Loss of solvent accessibility (P = 0.0079);.;.;
MVP		0.040
MPC		0.0078
ClinPred		0.13	T
GERP RS		-3.9
Varity_R		0.041
gMVP		0.44

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: chr16-75573923;