12-27697223-A-T

Variant names:

• chr12-27697223-A-T
• rs778864253
• NM_001029874.3:c.661A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001029874.3(REP15):​c.661A>T​(p.Lys221*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: REP15 NM_001029874.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REP15	NM_001029874.3	c.661A>T	p.Lys221*	stop_gained	Exon 1 of 1	ENST00000310791.4	NP_001025045.3
MRPS35-DT	XR_001749448.2	n.433-4681T>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REP15	ENST00000310791.4	c.661A>T	p.Lys221*	stop_gained	Exon 1 of 1	6	NM_001029874.3	ENSP00000310335.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.21
Eigen_PC	Benign	-0.062
FATHMM_MKL	Benign	0.31	N
Vest4		0.10
GERP RS		2.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs778864253; hg19: chr12-27850156;