2-88028379-C-A

Variant names:

• chr2-88028379-C-A
• NM_016618.3:c.185G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016618.3(KRCC1):​c.185G>T​(p.Arg62Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRCC1 NM_016618.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0570
• Publications: 0 publications found

Genes affected

KRCC1 (HGNC:28039): (lysine rich coiled-coil 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26018357).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016618.3. 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
	KRCC1	NM_016618.3	MANE Select	c.185G>T	p.Arg62Ile	missense	Exon 4 of 4	NP_057702.1	Q9NPI7
	KRCC1	NM_001304526.2		c.185G>T	p.Arg62Ile	missense	Exon 4 of 4	NP_001291455.1	Q9NPI7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRCC1	ENST00000347055.4	TSL:1 MANE Select	c.185G>T	p.Arg62Ile	missense	Exon 4 of 4	ENSP00000340083.3	Q9NPI7
	KRCC1	ENST00000672766.1		c.185G>T	p.Arg62Ile	missense	Exon 2 of 2	ENSP00000499834.1	Q9NPI7
	KRCC1	ENST00000910792.1		c.185G>T	p.Arg62Ile	missense	Exon 4 of 4	ENSP00000580851.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.057
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.16
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.015	D
Polyphen		0.94	P
Vest4		0.31
MutPred		0.33		Loss of disorder (P = 0.0159)
MVP		0.42
MPC		0.35
ClinPred		0.89	D
GERP RS		3.8
Varity_R		0.26
gMVP		0.12
Mutation Taster		=94/6	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

hg19: chr2-88327898;