rs11204846

Variant names:

• chr1-151543604-G-A
• rs11204846
• NM_020127.3:c.60+3178G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020127.3(TUFT1):​c.60+3178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,002 control chromosomes in the GnomAD database, including 10,572 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 0.37 (10572 hom., cov: 31)
• Consequence: TUFT1 NM_020127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.829
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUFT1	NM_020127.3	c.60+3178G>A		intron_variant	Intron 1 of 12	ENST00000368849.8	NP_064512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUFT1	ENST00000368849.8	c.60+3178G>A		intron_variant	Intron 1 of 12	1	NM_020127.3	ENSP00000357842.3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55750 AN: 151884 Hom.: 10567 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.0946

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.367 AC: 55769 AN: 152002 Hom.: 10572 Cov.: 31 AF XY: 0.362 AC XY: 26880 AN XY: 74272

African (AFR) AF: 0.356 AC: 14757 AN: 41438

American (AMR) AF: 0.296 AC: 4522 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1132 AN: 3468

East Asian (EAS) AF: 0.0946 AC: 490 AN: 5180

South Asian (SAS) AF: 0.332 AC: 1600 AN: 4822

European-Finnish (FIN) AF: 0.352 AC: 3717 AN: 10548

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28092 AN: 67970

Other (OTH) AF: 0.369 AC: 780 AN: 2112

Alfa AF: 0.389 Hom.: 1504

Bravo AF: 0.362

Asia WGS AF: 0.279 AC: 969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		0.83
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: rs11204846; hg19: chr1-151516080;