chr2-94871885-G-C

Position:

• chr2-94871885-G-C

Variant summary

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

The NM_144705.4(TEKT4):​c.306G>C​(p.Lys102Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: TEKT4 NM_144705.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17

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=0.379654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEKT4	NM_144705.4	c.306G>C	p.Lys102Asn	missense_variant	1/6	ENST00000295201.5	NP_653306.1
LOC442028	NR_037597.1	n.1318-1188C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEKT4	ENST00000295201.5	c.306G>C	p.Lys102Asn	missense_variant	1/6	1	NM_144705.4	ENSP00000295201	P1
	ENST00000568768.5	n.2225C>G		non_coding_transcript_exon_variant	8/8	1
TEKT4	ENST00000468063.1	n.453G>C		non_coding_transcript_exon_variant	1/6	2
	ENST00000582835.1	n.1317-1188C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152254 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 41

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74382

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.37
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.8	H
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.15
MutPred		0.51		Loss of ubiquitination at K102 (P = 0.0071);
MVP		0.45
MPC		0.24
ClinPred		1.0	D
GERP RS		2.0
Varity_R		0.41
gMVP		0.60

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: rs17802433; hg19: chr2-95537630;