chr3-51674425-C-G

Variant names:

• chr3-51674425-C-G
• rs199677902
• NM_015926.6:c.121C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015926.6(TEX264):​c.121C>G​(p.Pro41Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TEX264 NM_015926.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.03

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38473606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX264	NM_015926.6	c.121C>G	p.Pro41Ala	missense_variant	Exon 2 of 5	ENST00000341333.10	NP_057010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX264	ENST00000341333.10	c.121C>G	p.Pro41Ala	missense_variant	Exon 2 of 5	1	NM_015926.6	ENSP00000340969.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251408 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135906

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 SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.;T;T;T;.;T;T;T;T;T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;.;D;.;D;D;.;.;.;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.38	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	.;.;L;L;L;.;.;L;L;L;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.8	D;.;D;.;D;D;D;D;D;D;D;D
REVEL	Benign	0.15
Sift	Benign	0.078	T;.;D;.;D;T;T;D;D;D;T;T
Sift4G	Benign	0.15	T;D;T;T;T;T;T;T;T;T;T;T
Polyphen		1.0	.;.;D;D;D;.;.;D;D;D;.;.
Vest4		0.74, 0.59, 0.60
MutPred		0.36		Loss of disorder (P = 0.0747);Loss of disorder (P = 0.0747);Loss of disorder (P = 0.0747);Loss of disorder (P = 0.0747);Loss of disorder (P = 0.0747);Loss of disorder (P = 0.0747);Loss of disorder (P = 0.0747);Loss of disorder (P = 0.0747);Loss of disorder (P = 0.0747);Loss of disorder (P = 0.0747);Loss of disorder (P = 0.0747);Loss of disorder (P = 0.0747);
MVP		0.12
MPC		0.83
ClinPred		0.97	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.37
gMVP		0.77

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

LitVar

Other links and lift over

dbSNP: rs199677902; hg19: chr3-51708441;