1-151569700-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020127.3(TUFT1):​c.524C>T​(p.Thr175Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,613,904 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 11 hom., cov: 32)
Exomes 𝑓: 0.015 ( 225 hom. )

Consequence

TUFT1
NM_020127.3 missense

Scores

3
15

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.31
Variant links:
Genes affected
TUFT1 (HGNC:12422): (tuftelin 1) Tuftelin is an acidic protein that is thought to play a role in dental enamel mineralization and is implicated in caries susceptibility. It is also thought to be involved with adaptation to hypoxia, mesenchymal stem cell function, and neurotrophin nerve growth factor mediated neuronal differentiation. [provided by RefSeq, Aug 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0054446757).
BP6
Variant 1-151569700-C-T is Benign according to our data. Variant chr1-151569700-C-T is described in ClinVar as [Benign]. Clinvar id is 3770425.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0098 (1493/152278) while in subpopulation SAS AF= 0.0218 (105/4820). AF 95% confidence interval is 0.0184. There are 11 homozygotes in gnomad4. There are 764 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TUFT1NM_020127.3 linkc.524C>T p.Thr175Met missense_variant Exon 7 of 13 ENST00000368849.8 NP_064512.1 Q9NNX1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TUFT1ENST00000368849.8 linkc.524C>T p.Thr175Met missense_variant Exon 7 of 13 1 NM_020127.3 ENSP00000357842.3 Q9NNX1-1

Frequencies

GnomAD3 genomes
AF:
0.00979
AC:
1489
AN:
152160
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00304
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00975
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.0209
Gnomad FIN
AF:
0.0136
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0139
Gnomad OTH
AF:
0.00862
GnomAD3 exomes
AF:
0.0118
AC:
2968
AN:
251392
Hom.:
40
AF XY:
0.0130
AC XY:
1763
AN XY:
135852
show subpopulations
Gnomad AFR exome
AF:
0.00301
Gnomad AMR exome
AF:
0.00772
Gnomad ASJ exome
AF:
0.000595
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0216
Gnomad FIN exome
AF:
0.0137
Gnomad NFE exome
AF:
0.0141
Gnomad OTH exome
AF:
0.0142
GnomAD4 exome
AF:
0.0151
AC:
22028
AN:
1461626
Hom.:
225
Cov.:
31
AF XY:
0.0155
AC XY:
11254
AN XY:
727106
show subpopulations
Gnomad4 AFR exome
AF:
0.00236
Gnomad4 AMR exome
AF:
0.00743
Gnomad4 ASJ exome
AF:
0.000421
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0223
Gnomad4 FIN exome
AF:
0.0127
Gnomad4 NFE exome
AF:
0.0164
Gnomad4 OTH exome
AF:
0.0130
GnomAD4 genome
AF:
0.00980
AC:
1493
AN:
152278
Hom.:
11
Cov.:
32
AF XY:
0.0103
AC XY:
764
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00303
Gnomad4 AMR
AF:
0.00974
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.0218
Gnomad4 FIN
AF:
0.0136
Gnomad4 NFE
AF:
0.0139
Gnomad4 OTH
AF:
0.00853
Alfa
AF:
0.0129
Hom.:
31
Bravo
AF:
0.00898
TwinsUK
AF:
0.0148
AC:
55
ALSPAC
AF:
0.0215
AC:
83
ESP6500AA
AF:
0.00318
AC:
14
ESP6500EA
AF:
0.0133
AC:
114
ExAC
AF:
0.0121
AC:
1465
Asia WGS
AF:
0.00635
AC:
22
AN:
3478
EpiCase
AF:
0.0148
EpiControl
AF:
0.0130

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Feb 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

TUFT1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.063
T;T;.;T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.34
N
LIST_S2
Uncertain
0.93
D;D;D;D
MetaRNN
Benign
0.0054
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;.;.;.
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.1
N;N;N;.
REVEL
Benign
0.053
Sift
Benign
0.25
T;T;T;.
Sift4G
Uncertain
0.010
D;D;D;D
Polyphen
0.77
P;.;P;.
Vest4
0.30
MPC
0.25
ClinPred
0.014
T
GERP RS
3.4
Varity_R
0.039
gMVP
0.43

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: rs41310883; hg19: chr1-151542176; COSMIC: COSV61948026; COSMIC: COSV61948026; API