rs190390987

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001082538.3(TCTN1):​c.1379G>A​(p.Ser460Asn) 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 1,461,890 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

TCTN1
NM_001082538.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.258
Variant links:
Genes affected
TCTN1 (HGNC:26113): (tectonic family member 1) This gene encodes a member of a family of secreted and transmembrane proteins. The orthologous gene in mouse functions downstream of smoothened and rab23 to modulate hedgehog signal transduction. This protein is a component of the tectonic-like complex, which forms a barrier between the ciliary axoneme and the basal body. A mutation in this gene was found in a family with Joubert syndrome-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
HVCN1 (HGNC:28240): (hydrogen voltage gated channel 1) This gene encodes a voltage-gated protein channel protein expressed more highly in certain cells of the immune system. Phagocytic cells produce superoxide anions which require this channel protein, and in B cells this same process facilitates antibody production. This same channel protein, however, can also regulate functions in other cells including spermatozoa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

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ACMG classification

Classification made for transcript

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=0.02874431).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCTN1NM_001082538.3 linkc.1379G>A p.Ser460Asn missense_variant Exon 12 of 15 ENST00000397659.9 NP_001076007.1 Q2MV58-2B4DIB9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCTN1ENST00000397659.9 linkc.1379G>A p.Ser460Asn missense_variant Exon 12 of 15 1 NM_001082538.3 ENSP00000380779.4 Q2MV58-2
TCTN1ENST00000551590.5 linkc.1379G>A p.Ser460Asn missense_variant Exon 12 of 15 1 ENSP00000448735.1 Q2MV58-1
TCTN1ENST00000397655.7 linkc.1337G>A p.Ser446Asn missense_variant Exon 12 of 15 1 ENSP00000380775.3 Q2MV58-3
TCTN1ENST00000397656.8 linkn.*1012G>A non_coding_transcript_exon_variant Exon 13 of 16 2 ENSP00000380776.4 J3KPW2
TCTN1ENST00000480648.5 linkn.*655G>A non_coding_transcript_exon_variant Exon 13 of 16 5 ENSP00000437196.1 E9PNE4
TCTN1ENST00000495659.6 linkn.*1137G>A non_coding_transcript_exon_variant Exon 12 of 15 2 ENSP00000436673.2 E9PIB8
TCTN1ENST00000397656.8 linkn.*1012G>A 3_prime_UTR_variant Exon 13 of 16 2 ENSP00000380776.4 J3KPW2
TCTN1ENST00000480648.5 linkn.*655G>A 3_prime_UTR_variant Exon 13 of 16 5 ENSP00000437196.1 E9PNE4
TCTN1ENST00000495659.6 linkn.*1137G>A 3_prime_UTR_variant Exon 12 of 15 2 ENSP00000436673.2 E9PIB8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461890
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727246
show subpopulations
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
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
0.070
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
2.7
DANN
Benign
0.61
DEOGEN2
Benign
0.036
.;T;.;.;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.032
N
LIST_S2
Benign
0.54
T;T;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.029
T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.54
.;N;.;N;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.75
.;N;N;N;.
REVEL
Benign
0.086
Sift
Benign
1.0
.;T;T;T;.
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.0010
.;B;B;B;.
Vest4
0.068
MutPred
0.34
.;Gain of catalytic residue at Q456 (P = 0);.;Gain of catalytic residue at Q456 (P = 0);.;
MVP
0.44
MPC
0.18
ClinPred
0.016
T
GERP RS
-0.14
Varity_R
0.032
gMVP
0.29

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: chr12-111082819; API