NM_001077418.3:c.241C>G

Variant names:

• chr16-75555872-G-C
• NM_001077418.3:c.241C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001077418.3(TMEM231):​c.241C>G​(p.Leu81Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,438,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMEM231 NM_001077418.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28885084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM231	NM_001077418.3	c.241C>G	p.Leu81Val	missense_variant	Exon 2 of 7	ENST00000258173.11	NP_001070886.1
TMEM231	NM_001077416.2	c.400C>G	p.Leu134Val	missense_variant	Exon 1 of 6		NP_001070884.2
TMEM231	NR_074083.2	n.284C>G		non_coding_transcript_exon_variant	Exon 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM231	ENST00000258173.11	c.241C>G	p.Leu81Val	missense_variant	Exon 2 of 7	1	NM_001077418.3	ENSP00000258173.5
TMEM231	ENST00000568377.5	c.328C>G	p.Leu110Val	missense_variant	Exon 1 of 6	1		ENSP00000476267.1
TMEM231	ENST00000565067.5	c.241C>G	p.Leu81Val	missense_variant	Exon 2 of 6	5		ENSP00000457254.1
TMEM231	ENST00000562410.5	n.241C>G		non_coding_transcript_exon_variant	Exon 2 of 7	1		ENSP00000454582.1
TMEM231	ENST00000570006.5	n.241C>G		non_coding_transcript_exon_variant	Exon 2 of 7	5		ENSP00000455520.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438970 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 713190

Gnomad4 AFR exome AF: 0.0000304

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: 0.00

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
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.0012	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T;.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.88	L;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.85	N;.;N
REVEL	Benign	0.11
Sift	Benign	0.22	T;.;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.48	P;.;.
Vest4		0.38
MutPred		0.55		Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);
MVP		0.29
MPC		1.2
ClinPred		0.83	D
GERP RS		5.9
Varity_R		0.24
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-75589770;