dbSNP rs773514193: LRRCC1:p.Asp20Glu (chr8-85107355-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.65

Publications

0 publications found

Variant links:

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]

LRRCC1 links:

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

E2F5-DT links:

LOC105375933 (HGNC:):

LOC105375933 links:

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ACMG classification

Classification was made for transcript

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=0.1610592).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LRRCC1	NM_033402.5	MANE Select	c.60C>A	p.Asp20Glu	missense	Exon 1 of 19	NP_208325.3
LRRCC1	NM_001349636.2		c.-14C>A		5_prime_UTR	Exon 1 of 18	NP_001336565.1
LRRCC1	NM_001349637.2		c.-522C>A		5_prime_UTR	Exon 1 of 19	NP_001336566.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRCC1	ENST00000360375.8	TSL:1 MANE Select	c.60C>A	p.Asp20Glu	missense	Exon 1 of 19	ENSP00000353538.3	Q9C099-1
LRRCC1	ENST00000517875.5	TSL:1	n.60C>A		non_coding_transcript_exon	Exon 1 of 15	ENSP00000430960.1	E5RGA4
LRRCC1	ENST00000522567.5	TSL:1	n.60C>A		non_coding_transcript_exon	Exon 1 of 13	ENSP00000428794.1	E5RGA4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000162

AC:

AN:

247168

AF XY:

0.0000149

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461544

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.0000894

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111792

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0022

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.052

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.53

M_CAP

Benign

0.0048

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

1.7

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.68

REVEL

Benign

0.0090

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.72

Vest4

0.25

MutPred

0.36

Loss of sheet (P = 0.0817)

MVP

0.24

MPC

0.068

ClinPred

0.63

GERP RS

3.4

PromoterAI

-0.051

Neutral

(source)

Varity_R

0.32

gMVP

0.20

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over