rs1448792996

Variant names:

• chr7-100310387-G-A
• rs1448792996
• NM_001004351.5:c.353G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-100310387-G-A
• chr7-100310387-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004351.5(SPDYE3):​c.353G>A​(p.Arg118His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 13)
  • Exomes 𝑓: 0.000024 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE3 NM_001004351.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.564
• Publications: 0 publications found

Genes affected

SPDYE3 (HGNC:35462): (speedy/RINGO cell cycle regulator family member E3) Predicted to enable protein kinase binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291178 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.077239454).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004351.5. 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
	SPDYE3	NM_001004351.5	MANE Select	c.353G>A	p.Arg118His	missense	Exon 3 of 11	NP_001004351.3	A6NKU9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE3	ENST00000332397.6	TSL:1 MANE Select	c.353G>A	p.Arg118His	missense	Exon 3 of 11	ENSP00000329565.6	A6NKU9-1
	ENSG00000291178	ENST00000685541.3		n.658-9664C>T		intron	N/A
	ENSG00000291178	ENST00000685724.2		n.751-9664C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000269 AC: 3 AN: 111536 Hom.: 0 Cov.: 13

Gnomad AFR AF: 0.0000333

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000918 AC: 2 AN: 21796 AF XY: 0.0000879

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000348

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000238 AC: 20 AN: 841444 Hom.: 2 Cov.: 11 AF XY: 0.0000116 AC XY: 5 AN XY: 430382

African (AFR) AF: 0.00 AC: 0 AN: 20766

American (AMR) AF: 0.000378 AC: 8 AN: 21162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17488

East Asian (EAS) AF: 0.00 AC: 0 AN: 33790

South Asian (SAS) AF: 0.0000172 AC: 1 AN: 58292

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2810

European-Non Finnish (NFE) AF: 0.0000179 AC: 11 AN: 615894

Other (OTH) AF: 0.00 AC: 0 AN: 39052

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000269 AC: 3 AN: 111536 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 52566

African (AFR) AF: 0.0000333 AC: 1 AN: 30030

American (AMR) AF: 0.000196 AC: 2 AN: 10204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2836

East Asian (EAS) AF: 0.00 AC: 0 AN: 3756

South Asian (SAS) AF: 0.00 AC: 0 AN: 2890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52694

Other (OTH) AF: 0.00 AC: 0 AN: 1408

Alfa AF: 0.00 Hom.: 0

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	0.23
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.3
DANN	Benign	0.46
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.056	T
M_CAP	Benign	0.00073	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.56
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.037
Sift	Benign	0.33	T
Sift4G	Uncertain	0.042	D
Vest4		0.12
MutPred		0.30		Gain of catalytic residue at R118 (P = 0.023)
MVP		0.043
MPC		1.7
ClinPred		0.051	T
Varity_R		0.035
gMVP		0.0064
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1448792996; hg19: chr7-99908010;