chr7-100311771-C-A

Variant names:

• chr7-100311771-C-A
• rs1162757502
• NM_001004351.5:c.566C>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.566C>A​(p.Pro189His) 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 0.0000077 (0 hom., cov: 18)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE3 NM_001004351.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.872
• 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=0.100253314).

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.566C>A	p.Pro189His	missense	Exon 4 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.566C>A	p.Pro189His	missense	Exon 4 of 11	ENSP00000329565.6	A6NKU9-1
	ENSG00000291178	ENST00000685541.3		n.658-11048G>T		intron	N/A
	ENSG00000291178	ENST00000685724.2		n.751-11048G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000772 AC: 1 AN: 129544 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000203

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: 0.0000202 AC: 1 AN: 49498 AF XY: 0.0000401

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000130

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: 7.37e-7 AC: 1 AN: 1355998 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 675586

African (AFR) AF: 0.00 AC: 0 AN: 28182

American (AMR) AF: 0.00 AC: 0 AN: 42762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24048

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39476

South Asian (SAS) AF: 0.00 AC: 0 AN: 83062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3884

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1040954

Other (OTH) AF: 0.00 AC: 0 AN: 56594

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000772 AC: 1 AN: 129544 Hom.: 0 Cov.: 18 AF XY: 0.0000160 AC XY: 1 AN XY: 62474

African (AFR) AF: 0.00 AC: 0 AN: 31100

American (AMR) AF: 0.00 AC: 0 AN: 13266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2994

East Asian (EAS) AF: 0.000203 AC: 1 AN: 4920

South Asian (SAS) AF: 0.00 AC: 0 AN: 4190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8794

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61494

Other (OTH) AF: 0.00 AC: 0 AN: 1730

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	0.29
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.82
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.00081	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.87
PROVEAN	Benign	0.010	N
REVEL	Benign	0.020
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Vest4		0.28
MutPred		0.20		Loss of glycosylation at P189 (P = 0.0165)
MVP		0.043
MPC		1.9
ClinPred		0.079	T
Varity_R		0.079
gMVP		0.012
Mutation Taster		=300/0	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: rs1162757502; hg19: chr7-99909394;