3-113453524-T-C

Variant names:

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

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>G​(p.Glu695Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E695A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPICE1 NM_144718.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.2721871).

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>G	p.Glu695Gly	missense	Exon 14 of 18	NP_653319.1	Q8N0Z3
	SPICE1	NM_001331078.2		c.2084A>G	p.Glu695Gly	missense	Exon 14 of 18	NP_001318007.1	Q8N0Z3
	SPICE1	NM_001331079.2		c.2084A>G	p.Glu695Gly	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>G	p.Glu695Gly	missense	Exon 14 of 18	ENSP00000295872.4	Q8N0Z3
	SPICE1-CFAP44	ENST00000649772.1		n.2084A>G		non_coding_transcript_exon	Exon 14 of 39	ENSP00000497606.1
	SPICE1	ENST00000854922.1		c.2105A>G	p.Glu702Gly	missense	Exon 14 of 18	ENSP00000524981.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461728 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 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: 8.99e-7 AC: 1 AN: 1111904

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.4
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.15
Sift	Benign	0.054	T
Sift4G	Benign	0.070	T
Polyphen		1.0	D
Vest4		0.19
MutPred		0.23		Loss of solvent accessibility (P = 0.0769)
MVP		0.52
MPC		0.42
ClinPred		0.93	D
GERP RS		5.6
Varity_R		0.15
gMVP		0.091
Mutation Taster		=87/13	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;