1-36084950-G-A

Variant names:

• chr1-36084950-G-A
• rs367817474
• NM_014466.3:c.29G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014466.3(TEKT2):​c.29G>A​(p.Arg10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: TEKT2 NM_014466.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.71

Genes affected

TEKT2 (HGNC:11725): (tektin 2) 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 expressed in the testis and its protein is localized to the flagella of the sperms, indicating that it may play a role in spermatogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.011222273).
• BP6: Variant 1-36084950-G-A is Benign according to our data. Variant chr1-36084950-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3175741.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEKT2	NM_014466.3	c.29G>A	p.Arg10Gln	missense_variant	Exon 2 of 10	ENST00000207457.8	NP_055281.2
TEKT2	XM_005270753.3	c.29G>A	p.Arg10Gln	missense_variant	Exon 2 of 10		XP_005270810.1
TEKT2	XM_011541258.4	c.29G>A	p.Arg10Gln	missense_variant	Exon 2 of 10		XP_011539560.1
TEKT2	XM_017001055.2	c.29G>A	p.Arg10Gln	missense_variant	Exon 2 of 10		XP_016856544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEKT2	ENST00000207457.8	c.29G>A	p.Arg10Gln	missense_variant	Exon 2 of 10	1	NM_014466.3	ENSP00000207457.3
TEKT2	ENST00000469024.1	n.29G>A		non_coding_transcript_exon_variant	Exon 2 of 10	2		ENSP00000434183.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000187 AC: 47 AN: 251316 Hom.: 0 AF XY: 0.000236 AC XY: 32 AN XY: 135876

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00114

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000218 AC: 318 AN: 1461724 Hom.: 0 Cov.: 32 AF XY: 0.000274 AC XY: 199 AN XY: 727186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00133

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000176

Gnomad4 OTH exome AF: 0.0000994

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74484

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.000110

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000247 AC: 30

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 27, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.094	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-2.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.033
Sift	Benign	0.67	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.020
MVP		0.048
MPC		0.098
ClinPred		0.019	T
GERP RS		3.0
Varity_R		0.049
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs367817474; hg19: chr1-36550551;