1-151566219-C-A

Variant names:

• chr1-151566219-C-A
• NM_020127.3:c.471C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020127.3(TUFT1):​c.471C>A​(p.Ser157Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S157N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TUFT1 NM_020127.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.656

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08292344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUFT1	NM_020127.3	c.471C>A	p.Ser157Arg	missense_variant	Exon 6 of 13	ENST00000368849.8	NP_064512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUFT1	ENST00000368849.8	c.471C>A	p.Ser157Arg	missense_variant	Exon 6 of 13	1	NM_020127.3	ENSP00000357842.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459118 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725666

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Mar 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.471C>A (p.S157R) alteration is located in exon 6 (coding exon 6) of the TUFT1 gene. This alteration results from a C to A substitution at nucleotide position 471, causing the serine (S) at amino acid position 157 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.050	T;T;.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.083	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.56	N;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N;N;N;.
REVEL	Benign	0.052
Sift	Benign	0.21	T;T;T;.
Sift4G	Benign	0.48	T;T;T;T
Polyphen		0.0030	B;.;B;.
Vest4		0.23
MVP		0.22
MPC		0.21
ClinPred		0.11	T
GERP RS		3.0
Varity_R		0.075
gMVP		0.26

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: chr1-151538695;