chr12-27697232-G-C

Variant names:

• chr12-27697232-G-C
• rs559364694
• NM_001029874.3:c.670G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001029874.3(REP15):​c.670G>C​(p.Gly224Arg) 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. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G224E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: REP15 NM_001029874.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393
• Publications: 0 publications found

Genes affected

REP15 (HGNC:33748): (RAB15 effector protein) The protein encoded by this intronless gene interacts with GTP-bound Rab15 and is involved in recycling of transferrin receptor from the endocytic recycling compartment to the cell surface. [provided by RefSeq, Sep 2016]

MRPS35-DT (HGNC:55490): (MRPS35 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06348413).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029874.3. 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
	REP15	NM_001029874.3	MANE Select	c.670G>C	p.Gly224Arg	missense	Exon 1 of 1	NP_001025045.3	Q6BDI9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REP15	ENST00000310791.4	TSL:6 MANE Select	c.670G>C	p.Gly224Arg	missense	Exon 1 of 1	ENSP00000310335.2	Q6BDI9
	MRPS35-DT	ENST00000542660.1	TSL:3	n.360C>G		non_coding_transcript_exon	Exon 3 of 3
	MRPS35-DT	ENST00000536317.5	TSL:5	n.520-254C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.39
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.030
Sift	Benign	0.41	T
Sift4G	Benign	0.58	T
Polyphen		0.14	B
Vest4		0.12
MutPred		0.35		Gain of MoRF binding (P = 0.0172)
MVP		0.21
MPC		0.20
ClinPred		0.37	T
GERP RS		2.7
Varity_R		0.15
gMVP		0.48
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs559364694; hg19: chr12-27850165;