13-50015581-C-A

Variant names:

• chr13-50015581-C-A
• rs758273779
• NM_173605.2:c.88C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173605.2(KCNRG):​c.88C>A​(p.Arg30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R30C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KCNRG NM_173605.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 0 publications found

Genes affected

KCNRG (HGNC:18893): (potassium channel regulator) This gene encodes a protein which regulates the activity of voltage-gated potassium channels. This gene is on chromosome 13 and overlaps the gene for tripartite motif containing 13 on the same strand. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

TRIM13 (HGNC:9976): (tripartite motif containing 13) This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This gene is located on chromosome 13 within the minimal deletion region for B-cell chronic lymphocytic leukemia. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

DLEU2 (HGNC:13748): (deleted in lymphocytic leukemia 2) This locus represents a microRNA host gene and also produces long alternatively spliced non-coding RNAs. This genome region was observed to be deleted or epigenetically suppressed in leukemia, and was implicated as a negative regulator of cell proliferation. However, an alternative transcript produced at this locus was also found to promote progression through the cell cycle via angiotensin I converting enzyme 2 and cyclin D1. [provided by RefSeq, Dec 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173605.2. 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
	KCNRG	NM_173605.2	MANE Select	c.88C>A	p.Arg30Ser	missense	Exon 1 of 2	NP_775876.1	Q8N5I3-1
	TRIM13	NM_213590.3	MANE Select	c.*2417C>A		3_prime_UTR	Exon 2 of 2	NP_998755.1	O60858-1
	KCNRG	NM_199464.3		c.88C>A	p.Arg30Ser	missense	Exon 1 of 3	NP_955751.1	Q8N5I3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNRG	ENST00000312942.2	TSL:1 MANE Select	c.88C>A	p.Arg30Ser	missense	Exon 1 of 2	ENSP00000324191.1	Q8N5I3-1
	KCNRG	ENST00000360473.8	TSL:1	c.88C>A	p.Arg30Ser	missense	Exon 1 of 3	ENSP00000353661.4	Q8N5I3-2
	TRIM13	ENST00000378182.4	TSL:1 MANE Select	c.*2417C>A		3_prime_UTR	Exon 2 of 2	ENSP00000367424.3	O60858-1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461810 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727196

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	10
DANN	Benign	0.88
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.56
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.30
Sift	Benign	0.085	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.65
MutPred		0.54		Gain of catalytic residue at A28 (P = 0.0055)
MVP		0.66
MPC		0.16
ClinPred		0.47	T
GERP RS		1.0
PromoterAI		-0.069	Neutral
Varity_R		0.087
gMVP		0.61
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs758273779; hg19: chr13-50589717;