rs2337360

Variant names:

• chr1-151542127-G-A
• rs2337360
• NM_020127.3:c.60+1701G>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.60+1701G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,040 control chromosomes in the GnomAD database, including 9,433 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 0.34 (9433 hom., cov: 32)
• Consequence: TUFT1 NM_020127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 16 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000232536 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 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.60+1701G>A		intron	N/A	NP_064512.1	Q9NNX1-1
	TUFT1	NM_001301317.2		c.-23+1701G>A		intron	N/A	NP_001288246.1
	TUFT1	NM_001126337.2		c.60+1701G>A		intron	N/A	NP_001119809.1	Q9NNX1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUFT1	ENST00000368849.8	TSL:1 MANE Select	c.60+1701G>A		intron	N/A	ENSP00000357842.3	Q9NNX1-1
	TUFT1	ENST00000368848.6	TSL:1	c.60+1701G>A		intron	N/A	ENSP00000357841.2	Q9NNX1-2
	TUFT1	ENST00000873676.1		c.60+1701G>A		intron	N/A	ENSP00000543735.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52218 AN: 151920 Hom.: 9430 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.344 AC: 52235 AN: 152040 Hom.: 9433 Cov.: 32 AF XY: 0.339 AC XY: 25196 AN XY: 74316

African (AFR) AF: 0.274 AC: 11378 AN: 41456

American (AMR) AF: 0.288 AC: 4399 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3470

East Asian (EAS) AF: 0.0949 AC: 492 AN: 5186

South Asian (SAS) AF: 0.332 AC: 1597 AN: 4816

European-Finnish (FIN) AF: 0.353 AC: 3727 AN: 10564

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.413 AC: 28077 AN: 67962

Other (OTH) AF: 0.357 AC: 752 AN: 2108

Alfa AF: 0.388 Hom.: 34128

Bravo AF: 0.336

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.71
PhyloP100		-0.27
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: rs2337360; hg19: chr1-151514603;