1-151574349-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020127.3(TUFT1):c.674A>G(p.Lys225Arg) 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 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TUFT1 NM_020127.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056262016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUFT1	NM_020127.3	c.674A>G	p.Lys225Arg	missense_variant	8/13	ENST00000368849.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUFT1	ENST00000368849.8	c.674A>G	p.Lys225Arg	missense_variant	8/13	1	NM_020127.3	A1
TUFT1	ENST00000368848.6	c.599A>G	p.Lys200Arg	missense_variant	7/12	1		P4
TUFT1	ENST00000392712.7	c.509A>G	p.Lys170Arg	missense_variant	6/11	5
TUFT1	ENST00000490156.1	n.501A>G		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461884 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.674A>G (p.K225R) alteration is located in exon 8 (coding exon 8) of the TUFT1 gene. This alteration results from a A to G substitution at nucleotide position 674, causing the lysine (K) at amino acid position 225 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	0.093
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	17
Dann	Uncertain	0.98
DEOGEN2	Benign	0.080	T;T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	0.97	N;N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.77	N;N;N
REVEL	Benign	0.012
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.49	T;T;T
Polyphen		0.0020	B;.;B
Vest4		0.097
MVP		0.24
MPC		0.16
ClinPred		0.23	T
GERP RS		2.1
Varity_R		0.064
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr1-151546825;