NM_001080532.3:c.2459+336C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080532.3(TMC3):​c.2459+336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,086 control chromosomes in the GnomAD database, including 6,027 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 6027 hom., cov: 32)

Consequence

TMC3
NM_001080532.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00200

Publications

8 publications found
Variant links:
Genes affected
TMC3 (HGNC:22995): (transmembrane channel like 3) Predicted to enable mechanosensitive ion channel activity. Predicted to be involved in ion transmembrane transport. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
TMC3-AS1 (HGNC:51424): (TMC3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMC3NM_001080532.3 linkc.2459+336C>T intron_variant Intron 21 of 21 ENST00000359440.6 NP_001074001.1 Q7Z5M5-1
TMC3-AS1NR_120365.1 linkn.426+1843G>A intron_variant Intron 2 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMC3ENST00000359440.6 linkc.2459+336C>T intron_variant Intron 21 of 21 1 NM_001080532.3 ENSP00000352413.5 Q7Z5M5-1

Frequencies

GnomAD3 genomes
AF:
0.213
AC:
32370
AN:
151968
Hom.:
6009
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.509
Gnomad AMI
AF:
0.133
Gnomad AMR
AF:
0.110
Gnomad ASJ
AF:
0.124
Gnomad EAS
AF:
0.253
Gnomad SAS
AF:
0.117
Gnomad FIN
AF:
0.0690
Gnomad MID
AF:
0.180
Gnomad NFE
AF:
0.0890
Gnomad OTH
AF:
0.191
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.213
AC:
32434
AN:
152086
Hom.:
6027
Cov.:
32
AF XY:
0.209
AC XY:
15529
AN XY:
74376
show subpopulations
African (AFR)
AF:
0.509
AC:
21088
AN:
41438
American (AMR)
AF:
0.110
AC:
1681
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.124
AC:
429
AN:
3470
East Asian (EAS)
AF:
0.253
AC:
1304
AN:
5162
South Asian (SAS)
AF:
0.118
AC:
566
AN:
4814
European-Finnish (FIN)
AF:
0.0690
AC:
732
AN:
10604
Middle Eastern (MID)
AF:
0.167
AC:
49
AN:
294
European-Non Finnish (NFE)
AF:
0.0890
AC:
6049
AN:
67996
Other (OTH)
AF:
0.196
AC:
415
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1019
2039
3058
4078
5097
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
298
596
894
1192
1490
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.130
Hom.:
3950
Bravo
AF:
0.233
Asia WGS
AF:
0.194
AC:
676
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.50
DANN
Benign
0.27
PhyloP100
-0.0020
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs3935740; hg19: chr15-81626725; API