NM_178126.4:c.1076G>C

Variant names:

• chr17-42582138-C-G
• rs141966783
• NM_178126.4:c.1076G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178126.4(RETREG3):​c.1076G>C​(p.Arg359Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R359H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RETREG3 NM_178126.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• Publications: 5 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30803704).

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.1076G>C	p.Arg359Pro	missense	Exon 9 of 9	NP_835227.1	Q86VR2-1
	RETREG3	NR_026697.2		n.1148G>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.1076G>C	p.Arg359Pro	missense	Exon 9 of 9	ENSP00000309432.4	Q86VR2-1
	RETREG3	ENST00000585894.5	TSL:1	c.785G>C	p.Arg262Pro	missense	Exon 9 of 9	ENSP00000467847.1	K7EQI9
	RETREG3	ENST00000875458.1		c.1070G>C	p.Arg357Pro	missense	Exon 9 of 9	ENSP00000545517.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.84	T
PhyloP100		2.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Uncertain	0.022	D
Sift4G	Benign	0.088	T
Polyphen		1.0	D
Vest4		0.31
MutPred		0.27		Gain of glycosylation at R359 (P = 0.0057)
MVP		0.81
MPC		0.73
ClinPred		0.87	D
GERP RS		4.9
Varity_R		0.28
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141966783; hg19: chr17-40734156;