NM_001004351.5:c.440A>C

Variant names:

• chr7-100310474-A-C
• rs1192039636
• NM_001004351.5:c.440A>C

Variant summary

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

The NM_001004351.5(SPDYE3):​c.440A>C​(p.Glu147Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 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. E147G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 5)
  • Exomes 𝑓: 0.0000025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE3 NM_001004351.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• 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=0.112861484).

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.440A>C	p.Glu147Ala	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.440A>C	p.Glu147Ala	missense	Exon 3 of 11	ENSP00000329565.6	A6NKU9-1
	ENSG00000291178	ENST00000685541.3		n.658-9751T>G		intron	N/A
	ENSG00000291178	ENST00000685724.2		n.751-9751T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD2 exomes AF: 0.0000273 AC: 1 AN: 36686 AF XY: 0.00

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000253 AC: 1 AN: 395078 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 208352

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11178

American (AMR) AF: 0.00 AC: 0 AN: 17458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11764

East Asian (EAS) AF: 0.00 AC: 0 AN: 28452

South Asian (SAS) AF: 0.0000222 AC: 1 AN: 45122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 231804

Other (OTH) AF: 0.00 AC: 0 AN: 22542

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.00051	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.076
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.066
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Vest4		0.15
MutPred		0.17		Gain of glycosylation at T148 (P = 0.0523)
MVP		0.043
MPC		1.5
ClinPred		0.050	T
GERP RS		0.17
Varity_R		0.049
gMVP		0.013
Mutation Taster		=98/2	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: rs1192039636; hg19: chr7-99908097;