rs993305590

Variant names:

• chr8-85109742-C-A
• rs993305590
• NM_033402.5:c.252C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-85109742-C-A
• chr8-85109742-C-G
• chr8-85109742-C-T

Variant summary

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

The NM_033402.5(LRRCC1):​c.252C>A​(p.Asn84Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,450,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRRCC1 NM_033402.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

Genes affected

LRRCC1 (HGNC:29373): (leucine rich repeat and coiled-coil centrosomal protein 1) This gene encodes a centrosomal protein that maintains the structural integrity of the centrosome and plays a key role in mitotic spindle formation. The encoded protein contains an N-terminal leucine-rich repeat domain and a C-terminal coiled-coil domain. It associates with the centrosome throughout the cell cycle and accumulates on the mitotic centrosome. [provided by RefSeq, Mar 2017]

E2F5-DT (HGNC:55393): (E2F5 divergent transcript)

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=0.087893784).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033402.5. 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
	LRRCC1	NM_033402.5	MANE Select	c.252C>A	p.Asn84Lys	missense	Exon 2 of 19	NP_208325.3
	LRRCC1	NM_001349638.2		c.-260C>A		5_prime_UTR	Exon 2 of 17	NP_001336567.1
	LRRCC1	NM_001349636.2		c.32-373C>A		intron	N/A	NP_001336565.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRCC1	ENST00000360375.8	TSL:1 MANE Select	c.252C>A	p.Asn84Lys	missense	Exon 2 of 19	ENSP00000353538.3	Q9C099-1
	LRRCC1	ENST00000414626.2	TSL:1	c.192C>A	p.Asn64Lys	missense	Exon 1 of 18	ENSP00000394695.2	Q9C099-2
	LRRCC1	ENST00000517875.5	TSL:1	n.105-373C>A		intron	N/A	ENSP00000430960.1	E5RGA4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1450208 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 721940

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33256

American (AMR) AF: 0.00 AC: 0 AN: 44258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39442

South Asian (SAS) AF: 0.00 AC: 0 AN: 85262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102924

Other (OTH) AF: 0.00 AC: 0 AN: 59994

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.24	N
PhyloP100		1.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.081
Sift	Benign	0.077	T
Sift4G	Uncertain	0.059	T
Polyphen		0.0090	B
Vest4		0.26
MutPred		0.63		Gain of ubiquitination at N84 (P = 0.0592)
MVP		0.055
MPC		0.092
ClinPred		0.14	T
GERP RS		2.9
Varity_R		0.087
gMVP		0.22
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs993305590; hg19: chr8-86021977;