rs7554707

Variant names:

• chr1-151569239-G-T
• rs7554707
• NM_020127.3:c.481-418G>T

Variant summary

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

The NM_020127.3(TUFT1):​c.481-418G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,974 control chromosomes in the GnomAD database, including 25,742 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 0.56 (25742 hom., cov: 31)
• Consequence: TUFT1 NM_020127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUFT1	NM_020127.3	c.481-418G>T		intron_variant	Intron 6 of 12	ENST00000368849.8	NP_064512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUFT1	ENST00000368849.8	c.481-418G>T		intron_variant	Intron 6 of 12	1	NM_020127.3	ENSP00000357842.3

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85458 AN: 151856 Hom.: 25751 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.604

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.562 AC: 85478 AN: 151974 Hom.: 25742 Cov.: 31 AF XY: 0.556 AC XY: 41279 AN XY: 74264

African (AFR) AF: 0.355 AC: 14704 AN: 41436

American (AMR) AF: 0.594 AC: 9065 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2394 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1890 AN: 5150

South Asian (SAS) AF: 0.508 AC: 2449 AN: 4822

European-Finnish (FIN) AF: 0.562 AC: 5930 AN: 10548

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47038 AN: 67964

Other (OTH) AF: 0.605 AC: 1280 AN: 2114

Alfa AF: 0.653 Hom.: 56327

Bravo AF: 0.551

Asia WGS AF: 0.456 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.61
PhyloP100		-0.043
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: rs7554707; hg19: chr1-151541715;