NM_178126.4:c.1286G>C

Variant names:

• chr17-42581928-C-G
• rs965082838
• NM_178126.4:c.1286G>C

Variant summary

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

The NM_178126.4(RETREG3):​c.1286G>C​(p.Gly429Ala) 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. 15/21 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: RETREG3 NM_178126.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29
• Publications: 0 publications found

Genes affected

RETREG3 (HGNC:27258): (reticulophagy regulator family member 3) Involved in positive regulation of neuron projection development. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08004132).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178126.4. 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
	RETREG3	NM_178126.4	MANE Select	c.1286G>C	p.Gly429Ala	missense	Exon 9 of 9	NP_835227.1	Q86VR2-1
	RETREG3	NR_026697.2		n.1358G>C		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETREG3	ENST00000309428.10	TSL:1 MANE Select	c.1286G>C	p.Gly429Ala	missense	Exon 9 of 9	ENSP00000309432.4	Q86VR2-1
	RETREG3	ENST00000585894.5	TSL:1	c.995G>C	p.Gly332Ala	missense	Exon 9 of 9	ENSP00000467847.1	K7EQI9
	RETREG3	ENST00000875458.1		c.1280G>C	p.Gly427Ala	missense	Exon 9 of 9	ENSP00000545517.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.091
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.094
Sift	Benign	0.47	T
Sift4G	Benign	0.81	T
Polyphen		0.11	B
Vest4		0.031
MutPred		0.13		Gain of helix (P = 0.0425)
MVP		0.67
MPC		0.15
ClinPred		0.15	T
GERP RS		5.9
Varity_R		0.019
gMVP		0.15

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: rs965082838; hg19: chr17-40733946;