12-27696924-T-C

Position:

• chr12-27696924-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001029874.3(REP15):​c.362T>C​(p.Val121Ala) 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: REP15 NM_001029874.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0740

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040713012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REP15	NM_001029874.3	c.362T>C	p.Val121Ala	missense_variant	1/1	ENST00000310791.4	NP_001025045.3
MRPS35-DT	XR_001749448.2	n.433-4382A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REP15	ENST00000310791.4	c.362T>C	p.Val121Ala	missense_variant	1/1	6	NM_001029874.3	ENSP00000310335.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Jan 26, 2022

The c.362T>C (p.V121A) alteration is located in exon 1 (coding exon 1) of the REP15 gene. This alteration results from a T to C substitution at nucleotide position 362, causing the valine (V) at amino acid position 121 to be replaced by an alanine (A). 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	0.083
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.8
DANN	Benign	0.66
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.10
Sift	Benign	0.82	T
Sift4G	Benign	0.85	T
Polyphen		0.0	B
Vest4		0.062
MutPred		0.14		Gain of glycosylation at P120 (P = 0.0882);
MVP		0.030
MPC		0.17
ClinPred		0.049	T
GERP RS		1.4
Varity_R		0.034
gMVP		0.035

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-27849857;