1-151540419-A-G

Variant names:

• chr1-151540419-A-G
• rs3828054
• NM_020127.3:c.53A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020127.3(TUFT1):​c.53A>G​(p.Gln18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,936 control chromosomes in the GnomAD database, including 12,030 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1256 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10774 hom.)
• Consequence: TUFT1 NM_020127.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 20 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000232536 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011017025).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

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.53A>G	p.Gln18Arg	missense	Exon 1 of 13	NP_064512.1
	TUFT1	NM_001126337.2		c.53A>G	p.Gln18Arg	missense	Exon 1 of 12	NP_001119809.1
	TUFT1	NM_001301317.2		c.-30A>G		5_prime_UTR	Exon 1 of 14	NP_001288246.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUFT1	ENST00000368849.8	TSL:1 MANE Select	c.53A>G	p.Gln18Arg	missense	Exon 1 of 13	ENSP00000357842.3
	TUFT1	ENST00000368848.6	TSL:1	c.53A>G	p.Gln18Arg	missense	Exon 1 of 12	ENSP00000357841.2
	TUFT1	ENST00000873676.1		c.53A>G	p.Gln18Arg	missense	Exon 1 of 13	ENSP00000543735.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19414 AN: 152172 Hom.: 1258 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0557

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.114 AC: 28561 AN: 250812 AF XY: 0.113

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.0699

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.0522

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.118 AC: 172978 AN: 1461646 Hom.: 10774 Cov.: 32 AF XY: 0.117 AC XY: 85415 AN XY: 727136

African (AFR) AF: 0.145 AC: 4853 AN: 33470

American (AMR) AF: 0.0727 AC: 3253 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3260 AN: 26130

East Asian (EAS) AF: 0.0557 AC: 2209 AN: 39684

South Asian (SAS) AF: 0.101 AC: 8745 AN: 86242

European-Finnish (FIN) AF: 0.191 AC: 10219 AN: 53400

Middle Eastern (MID) AF: 0.0879 AC: 507 AN: 5766

European-Non Finnish (NFE) AF: 0.120 AC: 133068 AN: 1111854

Other (OTH) AF: 0.114 AC: 6864 AN: 60380

GnomAD4 genome AF: 0.127 AC: 19415 AN: 152290 Hom.: 1256 Cov.: 33 AF XY: 0.130 AC XY: 9709 AN XY: 74464

African (AFR) AF: 0.148 AC: 6141 AN: 41562

American (AMR) AF: 0.0863 AC: 1321 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3468

East Asian (EAS) AF: 0.0558 AC: 289 AN: 5176

South Asian (SAS) AF: 0.102 AC: 494 AN: 4832

European-Finnish (FIN) AF: 0.201 AC: 2126 AN: 10602

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8125 AN: 68030

Other (OTH) AF: 0.105 AC: 221 AN: 2114

Alfa AF: 0.117 Hom.: 4755

Bravo AF: 0.122

TwinsUK AF: 0.115 AC: 425

ALSPAC AF: 0.119 AC: 458

ESP6500AA AF: 0.154 AC: 678

ESP6500EA AF: 0.124 AC: 1069

ExAC AF: 0.116 AC: 14059

Asia WGS AF: 0.106 AC: 369 AN: 3478

EpiCase AF: 0.110

EpiControl AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.7
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.068
Sift	Benign	0.49	T
Sift4G	Benign	0.38	T
Polyphen		0.69	P
Vest4		0.23
MPC		0.21
ClinPred		0.012	T
GERP RS		2.5
PromoterAI		0.0046	Neutral
Varity_R		0.053
gMVP		0.15
Mutation Taster		=296/4	polymorphism (auto)

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

dbSNP: rs3828054; hg19: chr1-151512895; COSMIC: COSV54972332; COSMIC: COSV54972332;