rs956765904

Variant names:

• chr7-100308977-C-G
• rs956765904
• NM_001004351.5:c.110C>G

Variant summary

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

The NM_001004351.5(SPDYE3):​c.110C>G​(p.Pro37Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000024 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000042 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE3 NM_001004351.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.109
• 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=0.09961882).

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.110C>G	p.Pro37Arg	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.110C>G	p.Pro37Arg	missense	Exon 2 of 11	ENSP00000329565.6	A6NKU9-1
	ENSG00000291178	ENST00000685541.3		n.658-8254G>C		intron	N/A
	ENSG00000291178	ENST00000685724.2		n.751-8254G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000238 AC: 3 AN: 126192 Hom.: 0 Cov.: 17

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: 0.0000495

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000561 AC: 3 AN: 53464 AF XY: 0.0000372

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: 0.000149

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000422 AC: 19 AN: 450006 Hom.: 0 Cov.: 0 AF XY: 0.0000338 AC XY: 8 AN XY: 236950

African (AFR) AF: 0.00 AC: 0 AN: 12396

American (AMR) AF: 0.00 AC: 0 AN: 18930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13706

East Asian (EAS) AF: 0.00 AC: 0 AN: 31150

South Asian (SAS) AF: 0.00 AC: 0 AN: 45816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1964

European-Non Finnish (NFE) AF: 0.0000702 AC: 19 AN: 270514

Other (OTH) AF: 0.00 AC: 0 AN: 26066

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000238 AC: 3 AN: 126192 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 59550

African (AFR) AF: 0.00 AC: 0 AN: 32910

American (AMR) AF: 0.00 AC: 0 AN: 11496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3226

East Asian (EAS) AF: 0.00 AC: 0 AN: 4224

South Asian (SAS) AF: 0.00 AC: 0 AN: 3394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000495 AC: 3 AN: 60564

Other (OTH) AF: 0.00 AC: 0 AN: 1542

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	0.16
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.00075	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.11
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.053
Sift	Benign	0.063	T
Sift4G	Uncertain	0.010	D
Vest4		0.091
MutPred		0.25		Gain of methylation at P37 (P = 0.0138)
MVP		0.043
MPC		2.0
ClinPred		0.049	T
GERP RS		0.19
Varity_R		0.10
gMVP		0.031
Mutation Taster		=99/1	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: rs956765904; hg19: chr7-99906600;