chr5-34845636-C-T

Variant names:

• chr5-34845636-C-T
• rs766822648
• NM_144725.4:c.218C>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>T​(p.Ser73Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. S73Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• 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=0.14856136).

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>T	p.Ser73Phe	missense	Exon 3 of 11	NP_653326.3
	TTC23L	NM_001386170.1		c.218C>T	p.Ser73Phe	missense	Exon 3 of 11	NP_001373099.1
	TTC23L	NM_001386171.1		c.245C>T	p.Ser82Phe	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>T	p.Ser73Phe	missense	Exon 3 of 11	ENSP00000422188.1	Q6PF05-1
	TTC23L	ENST00000610313.1	TSL:1	c.218C>T	p.Ser73Phe	missense	Exon 2 of 7	ENSP00000484792.1	Q6PF05-2
	TTC23L	ENST00000514080.2	TSL:2	c.218C>T	p.Ser73Phe	missense	Exon 2 of 10	ENSP00000497109.1	A0A3B3IS63

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247702 AF XY: 0.0000223

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460834 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 726650

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000930 AC: 8 AN: 86044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111652

Other (OTH) AF: 0.0000331 AC: 2 AN: 60334

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.26
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.16
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Benign	0.039	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.29
MutPred		0.38		Loss of phosphorylation at S73 (P = 0.026)
MVP		0.38
MPC		0.47
ClinPred		0.78	D
GERP RS		3.0
Varity_R		0.080
gMVP		0.32
Mutation Taster		=94/6	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;