1-151562680-C-G

Variant names:

• chr1-151562680-C-G
• NM_020127.3:c.231C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 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: 1.24
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• woolly hair-skin fragility syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020127.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUFT1	NM_020127.3	MANE Select	c.231C>G	p.Ile77Met	missense	Exon 3 of 13	NP_064512.1	Q9NNX1-1
	TUFT1	NM_001301317.2		c.288C>G	p.Ile96Met	missense	Exon 4 of 14	NP_001288246.1
	TUFT1	NM_001126337.2		c.156C>G	p.Ile52Met	missense	Exon 2 of 12	NP_001119809.1	Q9NNX1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUFT1	ENST00000368849.8	TSL:1 MANE Select	c.231C>G	p.Ile77Met	missense	Exon 3 of 13	ENSP00000357842.3	Q9NNX1-1
	TUFT1	ENST00000368848.6	TSL:1	c.156C>G	p.Ile52Met	missense	Exon 2 of 12	ENSP00000357841.2	Q9NNX1-2
	TUFT1	ENST00000873676.1		c.231C>G	p.Ile77Met	missense	Exon 3 of 13	ENSP00000543735.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	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
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

hg19: chr1-151535156;