2-88028331-G-A

Variant names:

• chr2-88028331-G-A
• NM_016618.3:c.233C>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.233C>T​(p.Pro78Leu) 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. 16/22 in silico tools predict 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: 3.22
• 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=0.07726067).

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.233C>T	p.Pro78Leu	missense	Exon 4 of 4	NP_057702.1	Q9NPI7
	KRCC1	NM_001304526.2		c.233C>T	p.Pro78Leu	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.233C>T	p.Pro78Leu	missense	Exon 4 of 4	ENSP00000340083.3	Q9NPI7
	KRCC1	ENST00000672766.1		c.233C>T	p.Pro78Leu	missense	Exon 2 of 2	ENSP00000499834.1	Q9NPI7
	KRCC1	ENST00000910792.1		c.233C>T	p.Pro78Leu	missense	Exon 4 of 4	ENSP00000580851.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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	0.089
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.065
Sift	Uncertain	0.018	D
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.071
MutPred		0.29		Loss of disorder (P = 0.0219)
MVP		0.36
MPC		0.17
ClinPred		0.17	T
GERP RS		3.8
Varity_R		0.057
gMVP		0.061
Mutation Taster		=99/1	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: chr2-88327850;