1-151562109-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020127.3(TUFT1):c.79A>G(p.Arg27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUFT1 NM_020127.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUFT1	NM_020127.3	c.79A>G	p.Arg27Gly	missense_variant	2/13	ENST00000368849.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUFT1	ENST00000368849.8	c.79A>G	p.Arg27Gly	missense_variant	2/13	1	NM_020127.3	A1
TUFT1	ENST00000368848.6	c.61-476A>G		intron_variant		1		P4
TUFT1	ENST00000392712.7	c.61-476A>G		intron_variant		5
TUFT1	ENST00000498606.5	n.112A>G		non_coding_transcript_exon_variant	2/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 22, 2023

The c.79A>G (p.R27G) alteration is located in exon 2 (coding exon 2) of the TUFT1 gene. This alteration results from a A to G substitution at nucleotide position 79, causing the arginine (R) at amino acid position 27 to be replaced by a glycine (G). 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	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.79
MVP		0.37
MPC		0.86
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.59
gMVP		0.81

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: chr1-151534585;