2-88028379-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRCC1	NM_016618.3	c.185G>T	p.Arg62Ile	missense_variant	Exon 4 of 4	ENST00000347055.4	NP_057702.1
KRCC1	NM_001304526.2	c.185G>T	p.Arg62Ile	missense_variant	Exon 4 of 4		NP_001291455.1
KRCC1	XM_017004292.3	c.185G>T	p.Arg62Ile	missense_variant	Exon 4 of 4		XP_016859781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRCC1	ENST00000347055.4	c.185G>T	p.Arg62Ile	missense_variant	Exon 4 of 4	1	NM_016618.3	ENSP00000340083.3
KRCC1	ENST00000672766.1	c.185G>T	p.Arg62Ile	missense_variant	Exon 2 of 2			ENSP00000499834.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.185G>T (p.R62I) alteration is located in exon 4 (coding exon 1) of the KRCC1 gene. This alteration results from a G to T substitution at nucleotide position 185, causing the arginine (R) at amino acid position 62 to be replaced by an isoleucine (I). 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	0.12
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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-88327898;