chr16-2460163-T-G

Position:

• chr16-2460163-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000361837.9(TEDC2):​c.19T>G​(p.Ser7Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEDC2 ENST00000361837.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.647

Genes affected

TEDC2 (HGNC:25849): (tubulin epsilon and delta complex 2) Predicted to be involved in positive regulation of smoothened signaling pathway. Predicted to be located in centriole and cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.068365306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEDC2	NM_025108.3	c.19T>G	p.Ser7Ala	missense_variant	1/10	ENST00000361837.9	NP_079384.2
TEDC2	XM_011522667.2	c.19T>G	p.Ser7Ala	missense_variant	1/9		XP_011520969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEDC2	ENST00000361837.9	c.19T>G	p.Ser7Ala	missense_variant	1/10	1	NM_025108.3	ENSP00000355022	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Sep 16, 2021

The c.19T>G (p.S7A) alteration is located in exon 1 (coding exon 1) of the C16orf59 gene. This alteration results from a T to G substitution at nucleotide position 19, causing the serine (S) at amino acid position 7 to be replaced by an alanine (A). 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	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T;T;T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.39	T;.;T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.068	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;N;N;N
PROVEAN	Benign	-0.49	N;N;N;.
REVEL	Benign	0.013
Sift	Benign	0.42	T;T;T;.
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.34	B;.;.;.
Vest4		0.099
MutPred		0.14		Loss of phosphorylation at S7 (P = 0.0457);Loss of phosphorylation at S7 (P = 0.0457);Loss of phosphorylation at S7 (P = 0.0457);Loss of phosphorylation at S7 (P = 0.0457);
MVP		0.53
MPC		0.48
ClinPred		0.22	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.068
gMVP		0.13

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: chr16-2510164;