17-8757460-A-C

Variant names:

• chr17-8757460-A-C
• rs778490157
• NM_001394956.1:c.142T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394956.1(SPDYE4):​c.142T>G​(p.Ser48Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,866 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. S48T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPDYE4 NM_001394956.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13600907).

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.142T>G	p.Ser48Ala	missense	Exon 2 of 7	NP_001381885.1	A6NLX3
	SPDYE4	NM_001128076.3		c.142T>G	p.Ser48Ala	missense	Exon 2 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.142T>G	p.Ser48Ala	missense	Exon 2 of 7	ENSP00000509506.1	A6NLX3
	SPDYE4	ENST00000328794.10	TSL:1	c.142T>G	p.Ser48Ala	missense	Exon 2 of 6	ENSP00000329522.6	A6NLX3
	SPDYE4	ENST00000582989.1	TSL:1	n.*21T>G		non_coding_transcript_exon	Exon 2 of 6	ENSP00000464038.1	J3QR45

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000424 AC: 1 AN: 235922 AF XY: 0.00000785

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 AF: 6.88e-7 AC: 1 AN: 1453866 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722116

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 43140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108128

Other (OTH) AF: 0.00 AC: 0 AN: 60208

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.6
DANN	Benign	0.97
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.58
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.089
Sift	Benign	0.043	D
Sift4G	Benign	0.066	T
Polyphen		0.98	D
Vest4		0.14
MutPred		0.073		Loss of phosphorylation at S48 (P = 0.0125)
MVP		0.15
MPC		0.073
ClinPred		0.16	T
GERP RS		-1.2
PromoterAI		0.020	Neutral
Varity_R		0.057
gMVP		0.035

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: rs778490157; hg19: chr17-8660778;