rs1192601296

Variant names:

• chr7-102553299-C-T
• rs1192601296
• NM_001396242.1:c.44C>T

Variant summary

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

The NM_001396242.1(SPDYE2):​c.44C>T​(p.Thr15Met) 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: 0)
  • Exomes 𝑓: 0.00044 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE2 NM_001396242.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.17
• Publications: 0 publications found

Genes affected

SPDYE2 (HGNC:33841): (speedy/RINGO cell cycle regulator family member E2) Predicted to enable protein kinase binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000270249 (HGNC:):

POLR2J3 (HGNC:33853): (RNA polymerase II subunit J3) This gene is a member of the RNA polymerase II subunit 11 gene family, which includes three genes in a cluster on chromosome 7q22.1 and a pseudogene on chromosome 7p13. The founding member of this family, DNA directed RNA polymerase II polypeptide J, has been shown to encode a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This locus produces multiple, alternatively spliced transcripts that potentially express isoforms with distinct C-termini compared to DNA directed RNA polymerase II polypeptide J. Most or all variants are spliced to include additional non-coding exons at the 3' end which makes them candidates for nonsense-mediated decay (NMD). Consequently, it is not known if this locus expresses a protein or proteins in vivo. [provided by RefSeq, Jul 2008]

POLR2J3-UPK3BL2 (HGNC:58364):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.028121352).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396242.1. 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
	SPDYE2	NM_001396242.1	MANE Select	c.44C>T	p.Thr15Met	missense	Exon 2 of 9	NP_001383171.1	Q495Y8-1
	SPDYE2	NM_001031618.3		c.44C>T	p.Thr15Met	missense	Exon 2 of 9	NP_001026789.2	Q495Y8-1
	POLR2J3-UPK3BL2	NR_173351.1		n.465-11637G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE2	ENST00000691607.2	MANE Select	c.44C>T	p.Thr15Met	missense	Exon 2 of 9	ENSP00000509749.1	Q495Y8-1
	ENSG00000270249	ENST00000514917.3	TSL:3	c.749-11637G>A		intron	N/A	ENSP00000423309.4	H0Y980
	POLR2J3	ENST00000513506.6	TSL:5	c.383-11637G>A		intron	N/A	ENSP00000421085.1	E7EWC6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 3550 Hom.: 0 Cov.: 0

Gnomad AFR 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: 0.000109 AC: 1 AN: 9184 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: 0.000671

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000443 AC: 20 AN: 45098 Hom.: 0 Cov.: 0 AF XY: 0.000372 AC XY: 9 AN XY: 24202

African (AFR) AF: 0.00 AC: 0 AN: 5564

American (AMR) AF: 0.000338 AC: 1 AN: 2956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 600

East Asian (EAS) AF: 0.00 AC: 0 AN: 5524

South Asian (SAS) AF: 0.00 AC: 0 AN: 8522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 192

European-Non Finnish (NFE) AF: 0.00104 AC: 18 AN: 17318

Other (OTH) AF: 0.000396 AC: 1 AN: 2526

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 3550 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1572

African (AFR) AF: 0.00 AC: 0 AN: 2622

American (AMR) AF: 0.00 AC: 0 AN: 290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 212

South Asian (SAS) AF: 0.00 AC: 0 AN: 78

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 62

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 18

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 226

Other (OTH) AF: 0.00 AC: 0 AN: 38

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	0.080
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.8
DANN	Benign	0.94
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00031	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-2.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.041
Sift	Benign	0.33	T
Sift4G	Benign	0.36	T
Polyphen		0.037	B
Vest4		0.086
MutPred		0.24		Gain of sheet (P = 0.0221)
MVP		0.014
ClinPred		0.069	T
Varity_R		0.024
gMVP		0.041
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: rs1192601296; hg19: chr7-102193746;