rs1351674250

Variant names:

• chr7-44002629-G-A
• rs1351674250
• NM_001378423.2:c.419G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378423.2(SPDYE1):​c.419G>A​(p.Cys140Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000438 in 1,597,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: SPDYE1 NM_001378423.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.790
• Publications: 0 publications found

Genes affected

SPDYE1 (HGNC:16408): (speedy/RINGO cell cycle regulator family member E1) This gene is located at chromosome 7p13 which is close to the Williams Beuren syndrome chromosome region 7q11.23. [provided by RefSeq, Jul 2008]

POLR2J4 (HGNC:):

POLR2J4 (HGNC:28195): (RNA polymerase II subunit J4 (pseudogene))

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16722211).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378423.2. 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
	SPDYE1	NM_001378423.2	MANE Select	c.419G>A	p.Cys140Tyr	missense	Exon 4 of 9	NP_001365352.1	A0A494C1S0
	SPDYE1	NM_175064.4		c.299G>A	p.Cys100Tyr	missense	Exon 2 of 7	NP_778234.2
	POLR2J4	NR_003655.3		n.489+10964C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE1	ENST00000693451.1	MANE Select	c.419G>A	p.Cys140Tyr	missense	Exon 4 of 9	ENSP00000509569.1	A0A494C1S0
	SPDYE1	ENST00000258704.3	TSL:1	c.299G>A	p.Cys100Tyr	missense	Exon 2 of 7	ENSP00000258704.3	Q8NFV5
	POLR2J4	ENST00000427076.5	TSL:1	n.444+10964C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151830 Hom.: 0 Cov.: 20

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 237544 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 AF: 0.00000415 AC: 6 AN: 1445276 Hom.: 0 Cov.: 32 AF XY: 0.00000417 AC XY: 3 AN XY: 719356

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4140

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111826

Other (OTH) AF: 0.00 AC: 0 AN: 60122

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151830 Hom.: 0 Cov.: 20 AF XY: 0.0000135 AC XY: 1 AN XY: 74128

African (AFR) AF: 0.00 AC: 0 AN: 41328

American (AMR) AF: 0.00 AC: 0 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.21
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.0
DANN	Benign	0.70
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.79
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.080
Sift	Benign	0.13	T
Sift4G	Benign	1.0	T
Polyphen		0.93	P
Vest4		0.22
MutPred		0.22		Loss of catalytic residue at W101 (P = 6e-04)
MVP		0.048
MPC		2.5
ClinPred		0.30	T
Varity_R		0.087
gMVP		0.014
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1351674250; hg19: chr7-44042228;