rs3748609

Variant names:

• chr1-151573968-G-A
• rs3748609
• NM_020127.3:c.595-302G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-151573968-G-A
• chr1-151573968-G-C

Variant summary

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

The NM_020127.3(TUFT1):​c.595-302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,924 control chromosomes in the GnomAD database, including 24,799 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 0.54 (24799 hom., cov: 31)
• Consequence: TUFT1 NM_020127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.686 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUFT1	NM_020127.3	MANE Select	c.595-302G>A		intron	N/A	NP_064512.1
	TUFT1	NM_001301317.2		c.652-302G>A		intron	N/A	NP_001288246.1
	TUFT1	NM_001126337.2		c.520-302G>A		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.595-302G>A		intron	N/A	ENSP00000357842.3
	TUFT1	ENST00000368848.6	TSL:1	c.520-302G>A		intron	N/A	ENSP00000357841.2
	TUFT1	ENST00000392712.7	TSL:5	c.430-302G>A		intron	N/A	ENSP00000376476.3

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82406 AN: 151806 Hom.: 24806 Cov.: 31

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.543 AC: 82422 AN: 151924 Hom.: 24799 Cov.: 31 AF XY: 0.537 AC XY: 39860 AN XY: 74248

African (AFR) AF: 0.285 AC: 11824 AN: 41452

American (AMR) AF: 0.589 AC: 8982 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2390 AN: 3460

East Asian (EAS) AF: 0.369 AC: 1899 AN: 5152

South Asian (SAS) AF: 0.505 AC: 2428 AN: 4804

European-Finnish (FIN) AF: 0.562 AC: 5922 AN: 10540

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 46992 AN: 67948

Other (OTH) AF: 0.598 AC: 1259 AN: 2106

Alfa AF: 0.600 Hom.: 3766

Bravo AF: 0.529

Asia WGS AF: 0.455 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.60
PhyloP100		-0.010
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: rs3748609; hg19: chr1-151546444;