2-88028109-C-G

Variant names:

• chr2-88028109-C-G
• NM_016618.3:c.455G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016618.3(KRCC1):​c.455G>C​(p.Ser152Thr) 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. 14/21 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: 1.67

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=0.1878599).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRCC1	NM_016618.3	c.455G>C	p.Ser152Thr	missense_variant	Exon 4 of 4	ENST00000347055.4	NP_057702.1
KRCC1	NM_001304526.2	c.455G>C	p.Ser152Thr	missense_variant	Exon 4 of 4		NP_001291455.1
KRCC1	XM_017004292.3	c.455G>C	p.Ser152Thr	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.455G>C	p.Ser152Thr	missense_variant	Exon 4 of 4	1	NM_016618.3	ENSP00000340083.3
KRCC1	ENST00000672766.1	c.455G>C	p.Ser152Thr	missense_variant	Exon 2 of 2			ENSP00000499834.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.455G>C (p.S152T) alteration is located in exon 4 (coding exon 1) of the KRCC1 gene. This alteration results from a G to C substitution at nucleotide position 455, causing the serine (S) at amino acid position 152 to be replaced by a threonine (T). 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	0.086
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.051	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.098
Sift	Benign	0.063	T
Sift4G	Benign	0.24	T
Polyphen		0.87	P
Vest4		0.12
MutPred		0.24		Gain of glycosylation at S152 (P = 0.0335);
MVP		0.47
MPC		0.53
ClinPred		0.63	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.031

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-88327628;