12-123672090-C-G

Variant names:

• chr12-123672090-C-G
• NM_024809.5:c.225C>G

Variant summary

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

The NM_024809.5(TCTN2):​c.225C>G​(p.Asn75Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 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. Synonymous variant affecting the same amino acid position (i.e. N75N) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TCTN2 NM_024809.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.841

Genes affected

TCTN2 (HGNC:25774): (tectonic family member 2) This gene encodes a type I membrane protein that belongs to the tectonic family. Studies in mice suggest that this protein may be involved in hedgehog signaling, and essential for ciliogenesis. Mutations in this gene are associated with Meckel syndrome type 8. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

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=0.11853576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCTN2	NM_024809.5	c.225C>G	p.Asn75Lys	missense_variant	Exon 3 of 18	ENST00000303372.7	NP_079085.2
TCTN2	NM_001143850.3	c.225C>G	p.Asn75Lys	missense_variant	Exon 3 of 18		NP_001137322.1
TCTN2	NM_001410989.1	c.225C>G	p.Asn75Lys	missense_variant	Exon 3 of 17		NP_001397918.1
TCTN2	XM_017019974.2	c.225C>G	p.Asn75Lys	missense_variant	Exon 3 of 17		XP_016875463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCTN2	ENST00000303372.7	c.225C>G	p.Asn75Lys	missense_variant	Exon 3 of 18	1	NM_024809.5	ENSP00000304941.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727240

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: 8.99e-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	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.72
DEOGEN2	Benign	0.16	.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.23	T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.11
Sift	Benign	0.46	T;T
Sift4G	Benign	0.67	T;T
Polyphen		0.010	.;B
Vest4		0.20
MutPred		0.30		Gain of catalytic residue at V73 (P = 0.0011);Gain of catalytic residue at V73 (P = 0.0011);
MVP		0.66
MPC		0.18
ClinPred		0.026	T
GERP RS		0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.044
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr12-124156637;