7-100310387-G-C

Variant names:

• chr7-100310387-G-C
• rs1448792996
• NM_001004351.5:c.353G>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.353G>C​(p.Arg118Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 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. R118H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 13)
  • Exomes 𝑓: 0.0000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE3 NM_001004351.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• 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=0.104198426).

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.353G>C	p.Arg118Pro	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.353G>C	p.Arg118Pro	missense	Exon 3 of 11	ENSP00000329565.6	A6NKU9-1
	ENSG00000291178	ENST00000685541.3		n.658-9664C>G		intron	N/A
	ENSG00000291178	ENST00000685724.2		n.751-9664C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000119 AC: 1 AN: 841446 Hom.: 0 Cov.: 11 AF XY: 0.00000232 AC XY: 1 AN XY: 430382

⚠️ 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: 20768

American (AMR) AF: 0.00 AC: 0 AN: 21162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17488

East Asian (EAS) AF: 0.00 AC: 0 AN: 33790

South Asian (SAS) AF: 0.00 AC: 0 AN: 58292

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2810

European-Non Finnish (NFE) AF: 0.00000162 AC: 1 AN: 615894

Other (OTH) AF: 0.00 AC: 0 AN: 39052

⚠️ 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.: 13

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.3
DANN	Benign	0.29
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.046	T
M_CAP	Benign	0.00063	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.56
PROVEAN	Benign	0.34	N
REVEL	Benign	0.082
Sift	Benign	0.35	T
Sift4G	Benign	1.0	T
Vest4		0.20
MutPred		0.29		Gain of glycosylation at R118 (P = 0.0065)
MVP		0.043
MPC		1.9
ClinPred		0.084	T
Varity_R		0.11
gMVP		0.0048
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1448792996; hg19: chr7-99908010;