22-46272395-A-G

Position:

• chr22-46272395-A-G

Variant summary

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

The NM_017931.4(TTC38):​c.172A>G​(p.Lys58Glu) 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. 13/21 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: TTC38 NM_017931.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

Genes affected

TTC38 (HGNC:26082): (tetratricopeptide repeat domain 38) Located in extracellular exosome. [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=0.12623319).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC38	NM_017931.4	c.172A>G	p.Lys58Glu	missense_variant	3/14	ENST00000381031.8	NP_060401.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC38	ENST00000381031.8	c.172A>G	p.Lys58Glu	missense_variant	3/14	1	NM_017931.4	ENSP00000370419.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jun 29, 2023

The c.172A>G (p.K58E) alteration is located in exon 3 (coding exon 3) of the TTC38 gene. This alteration results from a A to G substitution at nucleotide position 172, causing the lysine (K) at amino acid position 58 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	Benign	0.10
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.0081	T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.24	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.052	B;.
Vest4		0.27
MutPred		0.43		Loss of ubiquitination at K58 (P = 0.0155);Loss of ubiquitination at K58 (P = 0.0155);
MVP		0.44
MPC		0.29
ClinPred		0.38	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.37

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: chr22-46668292;