1-151562680-C-G

Position:

• chr1-151562680-C-G

Variant summary

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

The NM_020127.3(TUFT1):​c.231C>G​(p.Ile77Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUFT1 NM_020127.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUFT1	NM_020127.3	c.231C>G	p.Ile77Met	missense_variant	3/13	ENST00000368849.8	NP_064512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUFT1	ENST00000368849.8	c.231C>G	p.Ile77Met	missense_variant	3/13	1	NM_020127.3	ENSP00000357842.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Oct 25, 2024

The c.231C>G (p.I77M) alteration is located in exon 3 (coding exon 3) of the TUFT1 gene. This alteration results from a C to G substitution at nucleotide position 231, causing the isoleucine (I) at amino acid position 77 to be replaced by a methionine (M). 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	0.30
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T;T;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.6	M;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.0	N;N;N;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D;D;D;.
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.62
MVP		0.16
MPC		0.76
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.37
gMVP		0.55

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: chr1-151535156;