chr7-100310486-C-T

Variant names:

• chr7-100310486-C-T
• rs1170042621
• NM_001004351.5:c.452C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004351.5(SPDYE3):​c.452C>T​(p.Ala151Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 5)
  • Exomes 𝑓: 0.000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE3 NM_001004351.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.748
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049823344).

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.452C>T	p.Ala151Val	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.452C>T	p.Ala151Val	missense	Exon 3 of 11	ENSP00000329565.6	A6NKU9-1
	ENSG00000291178	ENST00000685541.3		n.658-9763G>A		intron	N/A
	ENSG00000291178	ENST00000685724.2		n.751-9763G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 18406 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 34262 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: 0.0000161 AC: 6 AN: 372286 Hom.: 0 Cov.: 0 AF XY: 0.0000152 AC XY: 3 AN XY: 196794

⚠️ 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: 10666

American (AMR) AF: 0.0000598 AC: 1 AN: 16732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10938

East Asian (EAS) AF: 0.00 AC: 0 AN: 26688

South Asian (SAS) AF: 0.000112 AC: 5 AN: 44600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1580

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 217072

Other (OTH) AF: 0.00 AC: 0 AN: 21134

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00819118), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 18406 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 7948

African (AFR) AF: 0.00 AC: 0 AN: 4982

American (AMR) AF: 0.00 AC: 0 AN: 1382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 626

East Asian (EAS) AF: 0.00 AC: 0 AN: 800

South Asian (SAS) AF: 0.00 AC: 0 AN: 514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 52

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 9272

Other (OTH) AF: 0.00 AC: 0 AN: 228

Alfa AF: 0.00 Hom.: 0

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	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.9
DANN	Benign	0.17
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.097	T
M_CAP	Benign	0.00059	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.75
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.056
Sift	Benign	0.81	T
Sift4G	Benign	0.33	T
Vest4		0.20
MutPred		0.16		Loss of disorder (P = 0.1364)
MVP		0.043
MPC		1.4
ClinPred		0.024	T
GERP RS		-0.33
Varity_R		0.037
gMVP		0.0060
Mutation Taster		=300/0	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: rs1170042621; hg19: chr7-99908109;