chr7-100309142-G-A

Variant names:

• chr7-100309142-G-A
• rs1222035675
• NM_001004351.5:c.275G>A

Variant summary

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

The NM_001004351.5(SPDYE3):​c.275G>A​(p.Arg92Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 7)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE3 NM_001004351.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• 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=0.15040371).

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.275G>A	p.Arg92Gln	missense	Exon 2 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.275G>A	p.Arg92Gln	missense	Exon 2 of 11	ENSP00000329565.6	A6NKU9-1
	ENSG00000291178	ENST00000685541.3		n.658-8419C>T		intron	N/A
	ENSG00000291178	ENST00000685724.2		n.751-8419C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 53848 Hom.: 0 Cov.: 7

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00 AC: 0 AN: 51440 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 444718 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 233574

African (AFR) AF: 0.00 AC: 0 AN: 12354

American (AMR) AF: 0.00 AC: 0 AN: 18724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13610

East Asian (EAS) AF: 0.00 AC: 0 AN: 30572

South Asian (SAS) AF: 0.00 AC: 0 AN: 45720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1934

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 267196

Other (OTH) AF: 0.00 AC: 0 AN: 25762

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 53848 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 22812

African (AFR) AF: 0.00 AC: 0 AN: 13798

American (AMR) AF: 0.00 AC: 0 AN: 4296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1564

East Asian (EAS) AF: 0.00 AC: 0 AN: 2310

South Asian (SAS) AF: 0.00 AC: 0 AN: 1480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 27458

Other (OTH) AF: 0.00 AC: 0 AN: 658

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	Uncertain	0.55
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.00079	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.0
PROVEAN	Benign	0.070	N
REVEL	Benign	0.053
Sift	Benign	0.088	T
Sift4G	Benign	0.21	T
Vest4		0.10
MutPred		0.33		Loss of MoRF binding (P = 0.0499)
MVP		0.043
MPC		2.3
ClinPred		0.20	T
GERP RS		0.57
Varity_R		0.084
gMVP		0.011
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1222035675; hg19: chr7-99906765;