chr17-6812923-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT1	NM_053285.2	c.760C>T	p.Arg254Cys	missense_variant	Exon 6 of 8	ENST00000338694.7	NP_444515.1
TEKT1	XM_011524027.4	c.760C>T	p.Arg254Cys	missense_variant	Exon 6 of 7		XP_011522329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT1	ENST00000338694.7	c.760C>T	p.Arg254Cys	missense_variant	Exon 6 of 8	1	NM_053285.2	ENSP00000341346.2

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

GnomAD3 exomes AF: 0.231 AC: 58050 AN: 251260 Hom.: 7492 AF XY: 0.228 AC XY: 30903 AN XY: 135800

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 SAS exome AF: 0.229

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

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.216

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

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.198

Alfa AF: 0.202 Hom.: 8503

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 v4.3

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;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.71	T;T
MetaRNN	Benign	0.0021	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.9	.;D
REVEL	Benign	0.080
Sift	Benign	0.13	.;T
Sift4G	Benign	0.12	T;T
Polyphen		0.037	.;B
Vest4		0.095
MPC		0.12
ClinPred		0.015	T
GERP RS		0.21
Varity_R		0.19
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs3744395; hg19: chr17-6716242; COSMIC: COSV58622608; COSMIC: COSV58622608;