chr1-151552082-T-C

Variant names:

• chr1-151552082-T-C
• rs7526319
• NM_020127.3:c.61-10009T>C

Variant summary

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

The ENST00000368849.8(TUFT1):​c.61-10009T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,060 control chromosomes in the GnomAD database, including 24,542 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 0.55 (24542 hom., cov: 31)
• Consequence: TUFT1 ENST00000368849.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412
• Publications: 9 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368849.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUFT1	NM_020127.3	MANE Select	c.61-10009T>C		intron	N/A	NP_064512.1
	TUFT1	NM_001301317.2		c.-22-9636T>C		intron	N/A	NP_001288246.1
	TUFT1	NM_001126337.2		c.61-10503T>C		intron	N/A	NP_001119809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUFT1	ENST00000368849.8	TSL:1 MANE Select	c.61-10009T>C		intron	N/A	ENSP00000357842.3
	TUFT1	ENST00000368848.6	TSL:1	c.61-10503T>C		intron	N/A	ENSP00000357841.2
	TUFT1	ENST00000392712.7	TSL:5	c.61-10503T>C		intron	N/A	ENSP00000376476.3

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84144 AN: 151938 Hom.: 24518 Cov.: 31

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.554 AC: 84198 AN: 152060 Hom.: 24542 Cov.: 31 AF XY: 0.562 AC XY: 41780 AN XY: 74328

African (AFR) AF: 0.375 AC: 15564 AN: 41460

American (AMR) AF: 0.673 AC: 10282 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2281 AN: 3472

East Asian (EAS) AF: 0.890 AC: 4602 AN: 5172

South Asian (SAS) AF: 0.666 AC: 3216 AN: 4826

European-Finnish (FIN) AF: 0.647 AC: 6841 AN: 10566

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39699 AN: 67976

Other (OTH) AF: 0.570 AC: 1202 AN: 2110

Alfa AF: 0.572 Hom.: 5135

Bravo AF: 0.549

Asia WGS AF: 0.693 AC: 2412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.3
DANN	Benign	0.80
PhyloP100		0.41
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: rs7526319; hg19: chr1-151524558;