rs369742090

Variant names:

• chr3-113453524-T-G
• rs369742090
• NM_144718.4:c.2084A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-113453524-T-G
• chr3-113453524-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144718.4(SPICE1):​c.2084A>C​(p.Glu695Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: SPICE1 NM_144718.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39
• Publications: 0 publications found

Genes affected

SPICE1 (HGNC:25083): (spindle and centriole associated protein 1) Involved in metaphase plate congression; mitotic spindle assembly; and regulation of centriole replication. Located in centriole; centrosome; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

SPICE1-CFAP44 (HGNC:58084):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2691786).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144718.4. 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
	SPICE1	NM_144718.4	MANE Select	c.2084A>C	p.Glu695Ala	missense	Exon 14 of 18	NP_653319.1	Q8N0Z3
	SPICE1	NM_001331078.2		c.2084A>C	p.Glu695Ala	missense	Exon 14 of 18	NP_001318007.1	Q8N0Z3
	SPICE1	NM_001331079.2		c.2084A>C	p.Glu695Ala	missense	Exon 14 of 18	NP_001318008.2	Q8N0Z3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPICE1	ENST00000295872.8	TSL:1 MANE Select	c.2084A>C	p.Glu695Ala	missense	Exon 14 of 18	ENSP00000295872.4	Q8N0Z3
	SPICE1-CFAP44	ENST00000649772.1		n.2084A>C		non_coding_transcript_exon	Exon 14 of 39	ENSP00000497606.1
	SPICE1	ENST00000854922.1		c.2105A>C	p.Glu702Ala	missense	Exon 14 of 18	ENSP00000524981.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251320 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461728 Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21 AN XY: 727134

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000423 AC: 47 AN: 1111904

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000487 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0097	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Benign	0.030	D
Sift4G	Uncertain	0.059	T
Polyphen		1.0	D
Vest4		0.23
MVP		0.55
MPC		0.41
ClinPred		0.70	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.11
Mutation Taster		=89/11	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: rs369742090; hg19: chr3-113172371;