chr10-88314537-G-T

Variant names:

• chr10-88314537-G-T
• rs531117505
• NM_001031709.3:c.805C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031709.3(RNLS):​c.805C>A​(p.Gln269Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15

Genes affected

RNLS (HGNC:25641): (renalase, FAD dependent amine oxidase) Enables several functions, including NADH binding activity; epinephrine binding activity; and monoamine oxidase activity. Involved in negative regulation of blood pressure and negative regulation of heart rate. Located in extracellular region. Implicated in essential hypertension and hypertension. Biomarker of end stage renal disease. [provided by Alliance of Genome Resources, Apr 2022]

LOC101929727 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35103518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.805C>A	p.Gln269Lys	missense_variant	Exon 6 of 7	ENST00000331772.9	NP_001026879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000331772.9	c.805C>A	p.Gln269Lys	missense_variant	Exon 6 of 7	1	NM_001031709.3	ENSP00000332530.4
RNLS	ENST00000371947.7	c.805C>A	p.Gln269Lys	missense_variant	Exon 6 of 7	2		ENSP00000361015.3
RNLS	ENST00000466945.5	n.788C>A		non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.33	.;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.38
Sift	Benign	0.30	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.86	P;P
Vest4		0.41
MutPred		0.52		Gain of ubiquitination at Q269 (P = 0.0539);Gain of ubiquitination at Q269 (P = 0.0539);
MVP		0.85
MPC		0.10
ClinPred		0.58	D
GERP RS		6.0
Varity_R		0.62
gMVP		0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs531117505; hg19: chr10-90074294;