rs201318763

Variant names:

• chr17-8755541-C-T
• rs201318763
• NM_001394956.1:c.464G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-8755541-C-T
• chr17-8755541-C-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001394956.1(SPDYE4):​c.464G>A​(p.Arg155His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,611,574 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (3 hom.)
• Consequence: SPDYE4 NM_001394956.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.177
• Publications: 4 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 -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.464G>A	p.Arg155His	missense	Exon 4 of 7	NP_001381885.1	A6NLX3
	SPDYE4	NM_001128076.3		c.464G>A	p.Arg155His	missense	Exon 4 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.464G>A	p.Arg155His	missense	Exon 4 of 7	ENSP00000509506.1	A6NLX3
	SPDYE4	ENST00000328794.10	TSL:1	c.464G>A	p.Arg155His	missense	Exon 4 of 6	ENSP00000329522.6	A6NLX3
	SPDYE4	ENST00000582989.1	TSL:1	n.*343G>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000464038.1	J3QR45

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000104 AC: 26 AN: 251024 AF XY: 0.000118

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000133 AC: 194 AN: 1459470 Hom.: 3 Cov.: 30 AF XY: 0.000136 AC XY: 99 AN XY: 726002

African (AFR) AF: 0.0000299 AC: 1 AN: 33400

American (AMR) AF: 0.0000224 AC: 1 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86178

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4414

European-Non Finnish (NFE) AF: 0.000163 AC: 181 AN: 1111468

Other (OTH) AF: 0.0000498 AC: 3 AN: 60198

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152104 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74290

African (AFR) AF: 0.0000483 AC: 2 AN: 41414

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000155 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	0.36
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Benign	0.46
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.18
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.058
Sift	Benign	0.13	T
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.33
MVP		0.088
MPC		0.13
ClinPred		0.65	D
GERP RS		0.74
Varity_R		0.10
gMVP		0.33
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: -21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201318763; hg19: chr17-8658859; COSMIC: COSV60905621;