rs4970957

Variant names:

• chr1-151544912-A-G
• rs4970957
• NM_020127.3:c.60+4486A>G

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+4486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,118 control chromosomes in the GnomAD database, including 3,140 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 0.17 (3140 hom., cov: 32)
• Consequence: TUFT1 NM_020127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 17 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 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+4486A>G		intron	N/A	NP_064512.1	Q9NNX1-1
	TUFT1	NM_001301317.2		c.-23+4486A>G		intron	N/A	NP_001288246.1
	TUFT1	NM_001126337.2		c.60+4486A>G		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+4486A>G		intron	N/A	ENSP00000357842.3	Q9NNX1-1
	TUFT1	ENST00000368848.6	TSL:1	c.60+4486A>G		intron	N/A	ENSP00000357841.2	Q9NNX1-2
	TUFT1	ENST00000873676.1		c.60+4486A>G		intron	N/A	ENSP00000543735.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25973 AN: 152000 Hom.: 3139 Cov.: 32

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.171 AC: 25983 AN: 152118 Hom.: 3140 Cov.: 32 AF XY: 0.181 AC XY: 13428 AN XY: 74334

African (AFR) AF: 0.0406 AC: 1686 AN: 41536

American (AMR) AF: 0.305 AC: 4660 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1251 AN: 3472

East Asian (EAS) AF: 0.474 AC: 2441 AN: 5148

South Asian (SAS) AF: 0.218 AC: 1049 AN: 4818

European-Finnish (FIN) AF: 0.252 AC: 2661 AN: 10558

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11621 AN: 67996

Other (OTH) AF: 0.206 AC: 434 AN: 2110

Alfa AF: 0.160 Hom.: 295

Bravo AF: 0.168

Asia WGS AF: 0.324 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.2
DANN	Benign	0.56
PhyloP100		1.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4970957;

hg19: chr1-151517388;