rs764534593

Variant names:

• chr17-8758304-C-A
• rs764534593
• NM_001394956.1:c.79G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-8758304-C-A
• chr17-8758304-C-T

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.79G>T​(p.Val27Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. V27M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SPDYE4 NM_001394956.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• 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=0.08890319).

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.79G>T	p.Val27Leu	missense	Exon 1 of 7	NP_001381885.1	A6NLX3
	SPDYE4	NM_001128076.3		c.79G>T	p.Val27Leu	missense	Exon 1 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.79G>T	p.Val27Leu	missense	Exon 1 of 7	ENSP00000509506.1	A6NLX3
	SPDYE4	ENST00000328794.10	TSL:1	c.79G>T	p.Val27Leu	missense	Exon 1 of 6	ENSP00000329522.6	A6NLX3
	SPDYE4	ENST00000582989.1	TSL:1	n.79G>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000464038.1	J3QR45

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1397292 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 689008

African (AFR) AF: 0.00 AC: 0 AN: 31546

American (AMR) AF: 0.00 AC: 0 AN: 35396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24952

East Asian (EAS) AF: 0.00 AC: 0 AN: 35716

South Asian (SAS) AF: 0.00 AC: 0 AN: 78704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078038

Other (OTH) AF: 0.00 AC: 0 AN: 57962

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.62
DANN	Benign	0.56
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.37
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.063
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.050	T
Polyphen		0.0	B
Vest4		0.080
MutPred		0.13		Loss of glycosylation at S23 (P = 0.2482)
MVP		0.040
MPC		0.084
ClinPred		0.78	D
GERP RS		-5.3
PromoterAI		-0.0081	Neutral
Varity_R		0.084
gMVP		0.054
Mutation Taster		=100/0	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: rs764534593; hg19: chr17-8661622;