rs766822648

Variant names:

• chr5-34845636-C-A
• rs766822648
• NM_144725.4:c.218C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-34845636-C-A
• chr5-34845636-C-T

Variant summary

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

The NM_144725.4(TTC23L):​c.218C>A​(p.Ser73Tyr) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S73F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TTC23L NM_144725.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.162
• Publications: 0 publications found

Genes affected

TTC23L (HGNC:26355): (tetratricopeptide repeat domain 23 like) Predicted to be located in cytoplasm; microtubule cytoskeleton; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000302680 (HGNC:):

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=0.17363322).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144725.4. 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
	TTC23L	NM_144725.4	MANE Select	c.218C>A	p.Ser73Tyr	missense	Exon 3 of 11	NP_653326.3
	TTC23L	NM_001386170.1		c.218C>A	p.Ser73Tyr	missense	Exon 3 of 11	NP_001373099.1
	TTC23L	NM_001386171.1		c.245C>A	p.Ser82Tyr	missense	Exon 3 of 10	NP_001373100.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC23L	ENST00000505624.6	TSL:1 MANE Select	c.218C>A	p.Ser73Tyr	missense	Exon 3 of 11	ENSP00000422188.1	Q6PF05-1
	TTC23L	ENST00000610313.1	TSL:1	c.218C>A	p.Ser73Tyr	missense	Exon 2 of 7	ENSP00000484792.1	Q6PF05-2
	TTC23L	ENST00000514080.2	TSL:2	c.218C>A	p.Ser73Tyr	missense	Exon 2 of 10	ENSP00000497109.1	A0A3B3IS63

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.16
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.14
Sift	Uncertain	0.027	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.33
MutPred		0.41		Loss of phosphorylation at S73 (P = 0.0333)
MVP		0.38
MPC		0.52
ClinPred		0.84	D
GERP RS		3.0
Varity_R		0.093
gMVP		0.33
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs766822648; hg19: chr5-34845741;