rs3748608

Variant names:

• chr1-151578844-G-A
• rs3748608
• NM_020127.3:c.924+18G>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.924+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 1,544,108 control chromosomes in the GnomAD database, including 335,994 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 0.56 (26072 hom., cov: 32)
  • Exomes 𝑓: 0.66 (309922 hom.)
• Consequence: TUFT1 NM_020127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUFT1	NM_020127.3	c.924+18G>A		intron_variant	Intron 10 of 12	ENST00000368849.8	NP_064512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUFT1	ENST00000368849.8	c.924+18G>A		intron_variant	Intron 10 of 12	1	NM_020127.3	ENSP00000357842.3
TUFT1	ENST00000368848.6	c.849+18G>A		intron_variant	Intron 9 of 11	1		ENSP00000357841.2
TUFT1	ENST00000392712.7	c.759+18G>A		intron_variant	Intron 8 of 10	5		ENSP00000376476.3

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85474 AN: 152014 Hom.: 26074 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.610

GnomAD2 exomes AF: 0.592 AC: 95960 AN: 162144 AF XY: 0.597

Gnomad AFR exome AF: 0.316

Gnomad AMR exome AF: 0.530

Gnomad ASJ exome AF: 0.718

Gnomad EAS exome AF: 0.369

Gnomad FIN exome AF: 0.570

Gnomad NFE exome AF: 0.700

Gnomad OTH exome AF: 0.656

GnomAD4 exome AF: 0.662 AC: 920946 AN: 1391976 Hom.: 309922 Cov.: 30 AF XY: 0.659 AC XY: 452976 AN XY: 686960

African (AFR) AF: 0.319 AC: 10054 AN: 31476

American (AMR) AF: 0.541 AC: 19410 AN: 35846

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 17865 AN: 24904

East Asian (EAS) AF: 0.424 AC: 15129 AN: 35646

South Asian (SAS) AF: 0.540 AC: 42700 AN: 79042

European-Finnish (FIN) AF: 0.574 AC: 27837 AN: 48474

Middle Eastern (MID) AF: 0.720 AC: 3979 AN: 5530

European-Non Finnish (NFE) AF: 0.696 AC: 747173 AN: 1073648

Other (OTH) AF: 0.641 AC: 36799 AN: 57410

GnomAD4 genome AF: 0.562 AC: 85507 AN: 152132 Hom.: 26072 Cov.: 32 AF XY: 0.555 AC XY: 41304 AN XY: 74370

African (AFR) AF: 0.332 AC: 13753 AN: 41470

American (AMR) AF: 0.597 AC: 9140 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2492 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1990 AN: 5174

South Asian (SAS) AF: 0.514 AC: 2479 AN: 4822

European-Finnish (FIN) AF: 0.568 AC: 6017 AN: 10590

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47615 AN: 67994

Other (OTH) AF: 0.611 AC: 1290 AN: 2110

Alfa AF: 0.659 Hom.: 45124

Bravo AF: 0.550

Asia WGS AF: 0.482 AC: 1680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.10
DANN	Benign	0.37
PhyloP100		-1.7
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: rs3748608; hg19: chr1-151551320; COSMIC: COSV107434370; COSMIC: COSV107434370;