rs3748609

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUFT1	NM_020127.3	c.595-302G>A		intron_variant		ENST00000368849.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUFT1	ENST00000368849.8	c.595-302G>A		intron_variant		1	NM_020127.3	A1
TUFT1	ENST00000368848.6	c.520-302G>A		intron_variant		1		P4
TUFT1	ENST00000392712.7	c.430-302G>A		intron_variant		5
TUFT1	ENST00000490156.1	n.422-302G>A		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.598

Alfa AF: 0.613 Hom.: 3735

Bravo AF: 0.529

Asia WGS AF: 0.455 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs3748609; hg19: chr1-151546444;