17-8753325-T-C

Variant names:

• chr17-8753325-T-C
• rs568809932
• NM_001394956.1:c.650A>G

Variant summary

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

The NM_001394956.1(SPDYE4):​c.650A>G​(p.Glu217Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000083 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE4 NM_001394956.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41
• Publications: 1 publications found

Genes affected

SPDYE4 (HGNC:35463): (speedy/RINGO cell cycle regulator family member E4) Predicted to enable protein kinase binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000297596 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.24114355).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394956.1. 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
	SPDYE4	NM_001394956.1	MANE Select	c.650A>G	p.Glu217Gly	missense	Exon 5 of 7	NP_001381885.1	A6NLX3
	SPDYE4	NM_001128076.3		c.650A>G	p.Glu217Gly	missense	Exon 5 of 7	NP_001121548.1	A6NLX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE4	ENST00000689094.1	MANE Select	c.650A>G	p.Glu217Gly	missense	Exon 5 of 7	ENSP00000509506.1	A6NLX3
	SPDYE4	ENST00000328794.10	TSL:1	c.650A>G	p.Glu217Gly	missense	Exon 5 of 6	ENSP00000329522.6	A6NLX3
	SPDYE4	ENST00000582989.1	TSL:1	n.*529A>G		non_coding_transcript_exon	Exon 5 of 6	ENSP00000464038.1	J3QR45

Frequencies

GnomAD3 genomes AF: 0.0000847 AC: 4 AN: 47202 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000606

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000329

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000888

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000508

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000552 AC: 1 AN: 181276 AF XY: 0.0000104

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000736

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: 0.00000831 AC: 9 AN: 1083484 Hom.: 0 Cov.: 42 AF XY: 0.00000936 AC XY: 5 AN XY: 534364

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26810

American (AMR) AF: 0.00 AC: 0 AN: 29638

Ashkenazi Jewish (ASJ) AF: 0.0000635 AC: 1 AN: 15750

East Asian (EAS) AF: 0.00 AC: 0 AN: 17932

South Asian (SAS) AF: 0.00 AC: 0 AN: 70354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4238

European-Non Finnish (NFE) AF: 0.00000825 AC: 7 AN: 848718

Other (OTH) AF: 0.0000248 AC: 1 AN: 40258

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000846 AC: 4 AN: 47268 Hom.: 0 Cov.: 0 AF XY: 0.0000895 AC XY: 2 AN XY: 22340

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000604 AC: 1 AN: 16544

American (AMR) AF: 0.000328 AC: 1 AN: 3046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1088

East Asian (EAS) AF: 0.000888 AC: 1 AN: 1126

South Asian (SAS) AF: 0.00 AC: 0 AN: 1162

European-Finnish (FIN) AF: 0.000508 AC: 1 AN: 1968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 62

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 21338

Other (OTH) AF: 0.00 AC: 0 AN: 656

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00553722), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000838 AC: 1

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	0.44
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.082
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.024	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		1.4
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Benign	0.067
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.43		Loss of disorder (P = 0.0872)
MVP		0.32
MPC		0.39
ClinPred		0.67	D
GERP RS		1.6
Varity_R		0.31
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs568809932; hg19: chr17-8656643;