chr3-113448060-C-T

Variant names:

• chr3-113448060-C-T
• rs147299017
• NM_144718.4:c.2404G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_144718.4(SPICE1):​c.2404G>A​(p.Val802Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,608,396 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: SPICE1 NM_144718.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.134
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04427117).

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.2404G>A	p.Val802Ile	missense	Exon 16 of 18	NP_653319.1	Q8N0Z3
	SPICE1	NM_001331078.2		c.2404G>A	p.Val802Ile	missense	Exon 16 of 18	NP_001318007.1	Q8N0Z3
	SPICE1	NM_001331079.2		c.2404G>A	p.Val802Ile	missense	Exon 16 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.2404G>A	p.Val802Ile	missense	Exon 16 of 18	ENSP00000295872.4	Q8N0Z3
	SPICE1-CFAP44	ENST00000649772.1		n.2404G>A		non_coding_transcript_exon	Exon 16 of 39	ENSP00000497606.1
	SPICE1	ENST00000854922.1		c.2425G>A	p.Val809Ile	missense	Exon 16 of 18	ENSP00000524981.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 151914 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000641 AC: 16 AN: 249520 AF XY: 0.0000668

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000130 AC: 190 AN: 1456482 Hom.: 0 Cov.: 31 AF XY: 0.000133 AC XY: 96 AN XY: 724316

African (AFR) AF: 0.0000900 AC: 3 AN: 33340

American (AMR) AF: 0.000135 AC: 6 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 84634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.000154 AC: 171 AN: 1109584

Other (OTH) AF: 0.000150 AC: 9 AN: 60140

GnomAD4 genome AF: 0.000105 AC: 16 AN: 151914 Hom.: 0 Cov.: 32 AF XY: 0.0000944 AC XY: 7 AN XY: 74174

African (AFR) AF: 0.0000484 AC: 2 AN: 41334

American (AMR) AF: 0.000328 AC: 5 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000131 Hom.: 0

Bravo AF: 0.000128

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000576 AC: 7

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	0.078
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.41	N
PhyloP100		0.13
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.091
Sift	Benign	0.44	T
Sift4G	Uncertain	0.055	T
Polyphen		0.0050	B
Vest4		0.055
MVP		0.43
MPC		0.063
ClinPred		0.031	T
GERP RS		-0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.084
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs147299017; hg19: chr3-113166907; COSMIC: COSV55622412; COSMIC: COSV55622412;