2-94872053-C-A

Position:

• chr2-94872053-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144705.4(TEKT4):​c.474C>A​(p.Asp158Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: TEKT4 NM_144705.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.627

Genes affected

TEKT4 (HGNC:31012): (tektin 4) Predicted to be involved in cilium assembly and cilium movement involved in cell motility. Predicted to act upstream of or within regulation of brood size. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4132252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEKT4	NM_144705.4	c.474C>A	p.Asp158Glu	missense_variant	1/6	ENST00000295201.5	NP_653306.1
LOC442028	NR_037597.1	n.1317+1336G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEKT4	ENST00000295201.5	c.474C>A	p.Asp158Glu	missense_variant	1/6	1	NM_144705.4	ENSP00000295201	P1
	ENST00000568768.5	n.2057G>T		non_coding_transcript_exon_variant	8/8	1
TEKT4	ENST00000468063.1	n.621C>A		non_coding_transcript_exon_variant	1/6	2
	ENST00000582835.1	n.1316+1336G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1398868 Hom.: 0 Cov.: 41 AF XY: 0.00000290 AC XY: 2 AN XY: 690250

Gnomad4 AFR exome AF: 0.0000314

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.474C>A (p.D158E) alteration is located in exon 1 (coding exon 1) of the TEKT4 gene. This alteration results from a C to A substitution at nucleotide position 474, causing the aspartic acid (D) at amino acid position 158 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.014
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	4.0	H
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.94		Gain of disorder (P = 0.0587);
MVP		0.38
MPC		0.21
ClinPred		1.0	D
GERP RS		0.89
Varity_R		0.72
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-95537798;