rs121909063

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1PM2PM5BP4

The NM_005422.4(TECTA):​c.5668C>A​(p.Arg1890Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,880 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1890C) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TECTA
NM_005422.4 missense

Scores

1
12
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43
Variant links:
Genes affected
TECTA (HGNC:11720): (tectorin alpha) The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major noncollagenous components of the tectorial membrane. Mutations in the TECTA gene have been shown to be responsible for autosomal dominant nonsyndromic hearing impairment and a recessive form of sensorineural pre-lingual non-syndromic deafness. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1
In a domain ZP (size 254) in uniprot entity TECTA_HUMAN there are 13 pathogenic changes around while only 3 benign (81%) in NM_005422.4
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr11-121168135-C-T is described in Lovd as [Likely_pathogenic].
BP4
Computational evidence support a benign effect (MetaRNN=0.3862435).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TECTANM_005422.4 linkuse as main transcriptc.5668C>A p.Arg1890Ser missense_variant 19/24 ENST00000392793.6 NP_005413.2
TBCEL-TECTANM_001378761.1 linkuse as main transcriptc.6610C>A p.Arg2204Ser missense_variant 25/30 NP_001365690.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TECTAENST00000392793.6 linkuse as main transcriptc.5668C>A p.Arg1890Ser missense_variant 19/245 NM_005422.4 ENSP00000376543 P4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461880
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727244
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
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
Pathogenic
0.84
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;.;T
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.92
.;D;D
M_CAP
Benign
0.081
D
MetaRNN
Benign
0.39
T;T;T
MetaSVM
Uncertain
-0.054
T
MutationAssessor
Benign
0.0
N;.;N
MutationTaster
Benign
0.94
D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.2
N;.;N
REVEL
Uncertain
0.50
Sift
Uncertain
0.0070
D;.;D
Sift4G
Uncertain
0.0070
D;.;D
Polyphen
0.98
D;.;D
Vest4
0.52
MutPred
0.63
Gain of glycosylation at R1890 (P = 0.0923);.;Gain of glycosylation at R1890 (P = 0.0923);
MVP
0.85
MPC
0.70
ClinPred
0.81
D
GERP RS
4.3
Varity_R
0.50
gMVP
0.41

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121909063; hg19: chr11-121038844; API