rs41310883

Variant names:

• chr1-151569700-C-T
• rs41310883
• NM_020127.3:c.524C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-151569700-C-T
• chr1-151569700-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_020127.3(TUFT1):​c.524C>T​(p.Thr175Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,613,904 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (11 hom., cov: 32)
  • Exomes 𝑓: 0.015 (225 hom.)
• Consequence: TUFT1 NM_020127.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.31
• Publications: 9 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)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054446757).
• BP6: Variant 1-151569700-C-T is Benign according to our data. Variant chr1-151569700-C-T is described in ClinVar as Benign. ClinVar VariationId is 3770425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0098 (1493/152278) while in subpopulation SAS AF = 0.0218 (105/4820). AF 95% confidence interval is 0.0184. There are 11 homozygotes in GnomAd4. There are 764 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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.524C>T	p.Thr175Met	missense	Exon 7 of 13	NP_064512.1	Q9NNX1-1
	TUFT1	NM_001301317.2		c.581C>T	p.Thr194Met	missense	Exon 8 of 14	NP_001288246.1
	TUFT1	NM_001126337.2		c.449C>T	p.Thr150Met	missense	Exon 6 of 12	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.524C>T	p.Thr175Met	missense	Exon 7 of 13	ENSP00000357842.3	Q9NNX1-1
	TUFT1	ENST00000368848.6	TSL:1	c.449C>T	p.Thr150Met	missense	Exon 6 of 12	ENSP00000357841.2	Q9NNX1-2
	TUFT1	ENST00000873676.1		c.524C>T	p.Thr175Met	missense	Exon 7 of 13	ENSP00000543735.1

Frequencies

GnomAD3 genomes AF: 0.00979 AC: 1489 AN: 152160 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00304

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00862

GnomAD2 exomes AF: 0.0118 AC: 2968 AN: 251392 AF XY: 0.0130

Gnomad AFR exome AF: 0.00301

Gnomad AMR exome AF: 0.00772

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0137

Gnomad NFE exome AF: 0.0141

Gnomad OTH exome AF: 0.0142

GnomAD4 exome AF: 0.0151 AC: 22028 AN: 1461626 Hom.: 225 Cov.: 31 AF XY: 0.0155 AC XY: 11254 AN XY: 727106

African (AFR) AF: 0.00236 AC: 79 AN: 33476

American (AMR) AF: 0.00743 AC: 332 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.0223 AC: 1923 AN: 86250

European-Finnish (FIN) AF: 0.0127 AC: 676 AN: 53390

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5768

European-Non Finnish (NFE) AF: 0.0164 AC: 18180 AN: 1111812

Other (OTH) AF: 0.0130 AC: 786 AN: 60390

GnomAD4 genome AF: 0.00980 AC: 1493 AN: 152278 Hom.: 11 Cov.: 32 AF XY: 0.0103 AC XY: 764 AN XY: 74460

African (AFR) AF: 0.00303 AC: 126 AN: 41576

American (AMR) AF: 0.00974 AC: 149 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4820

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 948 AN: 68028

Other (OTH) AF: 0.00853 AC: 18 AN: 2110

Alfa AF: 0.0129 Hom.: 59

Bravo AF: 0.00898

TwinsUK AF: 0.0148 AC: 55

ALSPAC AF: 0.0215 AC: 83

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.0133 AC: 114

ExAC AF: 0.0121 AC: 1465

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.0148

EpiControl AF: 0.0130

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.053
Sift	Benign	0.25	T
Sift4G	Uncertain	0.010	D
Polyphen		0.77	P
Vest4		0.30
MPC		0.25
ClinPred		0.014	T
GERP RS		3.4
Varity_R		0.039
gMVP		0.43
Mutation Taster		=91/9	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: rs41310883; hg19: chr1-151542176; COSMIC: COSV61948026; COSMIC: COSV61948026;