rs778916011

Variant names:

• chr17-6812952-C-A
• rs778916011
• NM_053285.2:c.731G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-6812952-C-A
• chr17-6812952-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_053285.2(TEKT1):​c.731G>T​(p.Arg244Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R244Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TEKT1 NM_053285.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07505113).

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.731G>T	p.Arg244Leu	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.731G>T	p.Arg244Leu	missense	Exon 6 of 8	ENSP00000341346.2	Q969V4
	TEKT1	ENST00000572291.1	TSL:5	c.116G>T	p.Arg39Leu	missense	Exon 2 of 3	ENSP00000458518.1	I3L122
	TEKT1	ENST00000571744.1	TSL:3	c.65G>T	p.Arg22Leu	missense	Exon 1 of 2	ENSP00000460197.2	I3L357

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461848 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.6
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.11
Sift	Benign	0.32	T
Sift4G	Uncertain	0.024	D
Polyphen		0.011	B
Vest4		0.47
MutPred		0.52		Loss of MoRF binding (P = 0.016)
MVP		0.16
MPC		0.21
ClinPred		0.14	T
GERP RS		1.4
PromoterAI		-0.018	Neutral
Varity_R		0.16
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs778916011; hg19: chr17-6716271;