17-8753359-G-T

Variant names:

• chr17-8753359-G-T
• rs754409502
• NM_001394956.1:c.616C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394956.1(SPDYE4):​c.616C>A​(p.Arg206Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000754 in 1,325,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R206C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: SPDYE4 NM_001394956.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05047837).

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.616C>A	p.Arg206Ser	missense	Exon 5 of 7	NP_001381885.1	A6NLX3
	SPDYE4	NM_001128076.3		c.616C>A	p.Arg206Ser	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.616C>A	p.Arg206Ser	missense	Exon 5 of 7	ENSP00000509506.1	A6NLX3
	SPDYE4	ENST00000328794.10	TSL:1	c.616C>A	p.Arg206Ser	missense	Exon 5 of 6	ENSP00000329522.6	A6NLX3
	SPDYE4	ENST00000582989.1	TSL:1	n.*495C>A		non_coding_transcript_exon	Exon 5 of 6	ENSP00000464038.1	J3QR45

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.54e-7 AC: 1 AN: 1325608 Hom.: 0 Cov.: 39 AF XY: 0.00000153 AC XY: 1 AN XY: 654976

African (AFR) AF: 0.00 AC: 0 AN: 30992

American (AMR) AF: 0.00 AC: 0 AN: 35360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21220

East Asian (EAS) AF: 0.00 AC: 0 AN: 28940

South Asian (SAS) AF: 0.00 AC: 0 AN: 81710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5146

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1027102

Other (OTH) AF: 0.0000192 AC: 1 AN: 52200

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.2
DANN	Benign	0.85
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0096	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.072
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.024
Sift	Benign	0.61	T
Sift4G	Benign	0.61	T
Polyphen		0.0080	B
Vest4		0.15
MutPred		0.32		Loss of MoRF binding (P = 0.0553)
MVP		0.067
MPC		0.090
ClinPred		0.21	T
GERP RS		-1.9
Varity_R		0.062
gMVP		0.13

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: rs754409502; hg19: chr17-8656677;