1-151561845-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020127.3(TUFT1):c.61-246G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 1,473,388 control chromosomes in the GnomAD database, including 320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (290 hom.)
• Consequence: TUFT1 NM_020127.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0400

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-151561845-G-A is Benign according to our data. Variant chr1-151561845-G-A is described in ClinVar as [Benign]. Clinvar id is 778237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUFT1	NM_020127.3	c.61-246G>A		intron_variant		ENST00000368849.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUFT1	ENST00000368849.8	c.61-246G>A		intron_variant		1	NM_020127.3	A1
	ENST00000434112.1	n.516G>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.00701 AC: 1067 AN: 152208 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0553

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.0246 AC: 3310 AN: 134602 Hom.: 180 AF XY: 0.0198 AC XY: 1442 AN XY: 72688

Gnomad AFR exome AF: 0.000885

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.000365

Gnomad EAS exome AF: 0.0561

Gnomad SAS exome AF: 0.00133

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000174

Gnomad OTH exome AF: 0.0172

GnomAD4 exome AF: 0.00441 AC: 5831 AN: 1321062 Hom.: 290 Cov.: 32 AF XY: 0.00409 AC XY: 2661 AN XY: 650814

Gnomad4 AFR exome AF: 0.000297

Gnomad4 AMR exome AF: 0.0983

Gnomad4 ASJ exome AF: 0.000387

Gnomad4 EAS exome AF: 0.0686

Gnomad4 SAS exome AF: 0.00171

Gnomad4 FIN exome AF: 0.0000362

Gnomad4 NFE exome AF: 0.0000905

Gnomad4 OTH exome AF: 0.00411

GnomAD4 genome AF: 0.00699 AC: 1064 AN: 152326 Hom.: 30 Cov.: 32 AF XY: 0.00795 AC XY: 592 AN XY: 74492

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.0464

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0552

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00393 Hom.: 3

Bravo AF: 0.0130

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.6
Dann	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs78802584; hg19: chr1-151534321;