chr3-51674470-C-A

Position:

• chr3-51674470-C-A

Variant summary

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

The NM_015926.6(TEX264):​c.166C>A​(p.Leu56Ile) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TEX264 NM_015926.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

Genes affected

TEX264 (HGNC:30247): (testis expressed 264, ER-phagy receptor) Enables signaling receptor activity. Involved in protein-DNA covalent cross-linking repair. Acts upstream of or within reticulophagy. Located in several cellular components, including autophagosome membrane; endoplasmic reticulum membrane; and replication fork. [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=0.14108163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX264	NM_015926.6	c.166C>A	p.Leu56Ile	missense_variant	2/5	ENST00000341333.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX264	ENST00000341333.10	c.166C>A	p.Leu56Ile	missense_variant	2/5	1	NM_015926.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Dec 15, 2022

The c.166C>A (p.L56I) alteration is located in exon 3 (coding exon 1) of the TEX264 gene. This alteration results from a C to A substitution at nucleotide position 166, causing the leucine (L) at amino acid position 56 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.051	T;.;T;T;T;.;T;T;T;T;T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.59	T;T;.;T;.;T;T;.;.;.;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.17	N;.;N;.;N;N;N;N;N;N;N;N
REVEL	Benign	0.036
Sift	Uncertain	0.0040	D;.;D;.;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.025	D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.0030	.;.;B;B;B;.;.;B;B;B;.;.
Vest4		0.22, 0.18, 0.20
MutPred		0.58		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.043
MPC		0.38
ClinPred		0.32	T
GERP RS		2.6
Varity_R		0.050
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-51708486;