Genetic Variant TUFT1:p.Thr175Met (chr1-151569700-C-T) – ACMG Classification: Benign (-14 pts)

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

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]

TUFT1 links:

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
TUFT1	NM_020127.3 link	c.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
TUFT1	ENST00000368849.8 link	c.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.:

Cov.:

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.:

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.:

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.:

Cov.:

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.:

Bravo

AF:

0.00898

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0215

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0133

AC:

114

ExAC

AF:

0.0121

AC:

1465

Asia WGS

AF:

0.00635

AC:

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

BayesDel_noAF

Benign

-0.52

CADD

Benign

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

LIST_S2

Uncertain

0.93

D;D;D;D

MetaRNN

Benign

0.0054

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.;.

PrimateAI

Benign

0.46

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over