rs3790506

Variant names:

• chr1-151565890-G-A
• rs3790506
• NM_020127.3:c.415-273G>A

Variant summary

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

The NM_020127.3(TUFT1):​c.415-273G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 328,736 control chromosomes in the GnomAD database, including 13,260 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5576 hom., cov: 32)
  • Exomes 𝑓: 0.28 (7684 hom.)
• Consequence: TUFT1 NM_020127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 24 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUFT1	NM_020127.3	c.415-273G>A		intron_variant	Intron 5 of 12	ENST00000368849.8	NP_064512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUFT1	ENST00000368849.8	c.415-273G>A		intron_variant	Intron 5 of 12	1	NM_020127.3	ENSP00000357842.3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38825 AN: 151794 Hom.: 5579 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.285 AC: 50318 AN: 176824 Hom.: 7684 Cov.: 0 AF XY: 0.286 AC XY: 26939 AN XY: 94048

African (AFR) AF: 0.126 AC: 768 AN: 6112

American (AMR) AF: 0.367 AC: 3134 AN: 8548

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 1128 AN: 5294

East Asian (EAS) AF: 0.270 AC: 3147 AN: 11658

South Asian (SAS) AF: 0.320 AC: 7442 AN: 23236

European-Finnish (FIN) AF: 0.230 AC: 1914 AN: 8310

Middle Eastern (MID) AF: 0.250 AC: 178 AN: 712

European-Non Finnish (NFE) AF: 0.290 AC: 30031 AN: 103398

Other (OTH) AF: 0.270 AC: 2576 AN: 9556

GnomAD4 genome AF: 0.256 AC: 38829 AN: 151912 Hom.: 5576 Cov.: 32 AF XY: 0.255 AC XY: 18966 AN XY: 74238

African (AFR) AF: 0.127 AC: 5277 AN: 41440

American (AMR) AF: 0.354 AC: 5398 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3468

East Asian (EAS) AF: 0.282 AC: 1456 AN: 5160

South Asian (SAS) AF: 0.360 AC: 1730 AN: 4804

European-Finnish (FIN) AF: 0.221 AC: 2337 AN: 10556

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20773 AN: 67932

Other (OTH) AF: 0.271 AC: 571 AN: 2108

Alfa AF: 0.297 Hom.: 10031

Bravo AF: 0.258

Asia WGS AF: 0.309 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.039
DANN	Benign	0.55
PhyloP100		-2.2
Mutation Taster		=100/0	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: rs3790506; hg19: chr1-151538366;