NM_001004351.5:c.398C>A

Variant names:

• chr7-100310432-C-A
• NM_001004351.5:c.398C>A

Variant summary

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

The NM_001004351.5(SPDYE3):​c.398C>A​(p.Ser133Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE3 NM_001004351.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.697
• Publications: 0 publications found

Genes affected

SPDYE3 (HGNC:35462): (speedy/RINGO cell cycle regulator family member E3) Predicted to enable protein kinase binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291178 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.1145736).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004351.5. 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
	SPDYE3	NM_001004351.5	MANE Select	c.398C>A	p.Ser133Tyr	missense	Exon 3 of 11	NP_001004351.3	A6NKU9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE3	ENST00000332397.6	TSL:1 MANE Select	c.398C>A	p.Ser133Tyr	missense	Exon 3 of 11	ENSP00000329565.6	A6NKU9-1
	ENSG00000291178	ENST00000685541.3		n.658-9709G>T		intron	N/A
	ENSG00000291178	ENST00000685724.2		n.751-9709G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 612482 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 317722

African (AFR) AF: 0.00 AC: 0 AN: 16066

American (AMR) AF: 0.00 AC: 0 AN: 18904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14392

East Asian (EAS) AF: 0.00 AC: 0 AN: 31610

South Asian (SAS) AF: 0.00 AC: 0 AN: 50668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 418656

Other (OTH) AF: 0.00 AC: 0 AN: 30590

GnomAD4 genome Cov.: 8

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	Benign	0.22
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.00092	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.70
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.049
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.036	D
Vest4		0.17
MutPred		0.17		Gain of helix (P = 0.062)
MVP		0.043
MPC		2.8
ClinPred		0.23	T
Varity_R		0.078
gMVP		0.0088
Mutation Taster		=97/3	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

hg19: chr7-99908055;