rs773514193

Variant names:

• chr8-85107355-C-A
• rs773514193
• NM_033402.5:c.60C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-85107355-C-A
• chr8-85107355-C-G
• chr8-85107355-C-T

Variant summary

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

The NM_033402.5(LRRCC1):​c.60C>A​(p.Asp20Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D20D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LRRCC1 NM_033402.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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]

LOC105375933 (HGNC:):

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=0.1610592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRCC1	NM_033402.5	c.60C>A	p.Asp20Glu	missense_variant	Exon 1 of 19	ENST00000360375.8	NP_208325.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRCC1	ENST00000360375.8	c.60C>A	p.Asp20Glu	missense_variant	Exon 1 of 19	1	NM_033402.5	ENSP00000353538.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000162 AC: 4 AN: 247168 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134378

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461544 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727084

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.0090
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.72	P
Vest4		0.25
MutPred		0.36		Loss of sheet (P = 0.0817);
MVP		0.24
MPC		0.068
ClinPred		0.63	D
GERP RS		3.4
Varity_R		0.32
gMVP		0.20

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

LitVar

Other links and lift over

dbSNP: rs773514193; hg19: chr8-86019590;