rs3744395

Variant names:

• chr17-6812923-G-A
• rs3744395
• NM_053285.2:c.760C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-6812923-G-A
• chr17-6812923-G-C
• chr17-6812923-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053285.2(TEKT1):​c.760C>T​(p.Arg254Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,613,926 control chromosomes in the GnomAD database, including 38,210 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R254H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.19 (3060 hom., cov: 33)
  • Exomes 𝑓: 0.21 (35150 hom.)
• Consequence: TEKT1 NM_053285.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.974
• Publications: 30 publications found

Genes affected

TEKT1 (HGNC:15534): (tektin 1) This gene product belongs to the tektin family of proteins. Tektins comprise a family of filament-forming proteins that are coassembled with tubulins to form ciliary and flagellar microtubules. This gene is predominantly expressed in the testis and in mouse, tektin 1 mRNA was localized to the spermatocytes and round spermatids in the seminiferous tubules, indicating that it may play a role in spermatogenesis. [provided by RefSeq, Jul 2008]

TEKT1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020502806).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053285.2. 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
	TEKT1	NM_053285.2	MANE Select	c.760C>T	p.Arg254Cys	missense	Exon 6 of 8	NP_444515.1	Q969V4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEKT1	ENST00000338694.7	TSL:1 MANE Select	c.760C>T	p.Arg254Cys	missense	Exon 6 of 8	ENSP00000341346.2	Q969V4
	TEKT1	ENST00000572291.1	TSL:5	c.145C>T	p.Arg49Cys	missense	Exon 2 of 3	ENSP00000458518.1	I3L122
	TEKT1	ENST00000571744.1	TSL:3	c.94C>T	p.Arg32Cys	missense	Exon 1 of 2	ENSP00000460197.2	I3L357

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28912 AN: 152080 Hom.: 3063 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.197

GnomAD2 exomes AF: 0.231 AC: 58050 AN: 251260 AF XY: 0.228

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.294

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.439

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.213 AC: 311558 AN: 1461728 Hom.: 35150 Cov.: 34 AF XY: 0.212 AC XY: 154156 AN XY: 727168

African (AFR) AF: 0.107 AC: 3582 AN: 33480

American (AMR) AF: 0.285 AC: 12759 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 4508 AN: 26134

East Asian (EAS) AF: 0.459 AC: 18210 AN: 39698

South Asian (SAS) AF: 0.228 AC: 19681 AN: 86256

European-Finnish (FIN) AF: 0.225 AC: 12017 AN: 53368

Middle Eastern (MID) AF: 0.120 AC: 692 AN: 5766

European-Non Finnish (NFE) AF: 0.204 AC: 227061 AN: 1111910

Other (OTH) AF: 0.216 AC: 13048 AN: 60392

GnomAD4 genome AF: 0.190 AC: 28914 AN: 152198 Hom.: 3060 Cov.: 33 AF XY: 0.193 AC XY: 14323 AN XY: 74388

African (AFR) AF: 0.113 AC: 4687 AN: 41550

American (AMR) AF: 0.234 AC: 3578 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2179 AN: 5166

South Asian (SAS) AF: 0.246 AC: 1184 AN: 4820

European-Finnish (FIN) AF: 0.205 AC: 2175 AN: 10590

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13900 AN: 67998

Other (OTH) AF: 0.198 AC: 417 AN: 2110

Alfa AF: 0.202 Hom.: 16815

Bravo AF: 0.191

TwinsUK AF: 0.208 AC: 772

ALSPAC AF: 0.193 AC: 744

ESP6500AA AF: 0.123 AC: 541

ESP6500EA AF: 0.207 AC: 1780

ExAC AF: 0.228 AC: 27734

Asia WGS AF: 0.317 AC: 1101 AN: 3478

EpiCase AF: 0.199

EpiControl AF: 0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.97
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.080
Sift	Benign	0.13	T
Sift4G	Benign	0.12	T
Polyphen		0.037	B
Vest4		0.095
MPC		0.12
ClinPred		0.015	T
GERP RS		0.21
PromoterAI		-0.075	Neutral
Varity_R		0.19
gMVP		0.52
Mutation Taster		=95/5	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: rs3744395; hg19: chr17-6716242; COSMIC: COSV58622608; COSMIC: COSV58622608;