7-44001092-T-A

Variant names:

• chr7-44001092-T-A
• rs572510223
• NM_001378423.2:c.187T>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.187T>A​(p.Cys63Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. C63R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPDYE1 NM_001378423.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• 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=0.07037929).

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.187T>A	p.Cys63Ser	missense	Exon 3 of 9	NP_001365352.1	A0A494C1S0
	SPDYE1	NM_175064.4		c.67T>A	p.Cys23Ser	missense	Exon 1 of 7	NP_778234.2
	POLR2J4	NR_003655.3		n.489+12501A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE1	ENST00000693451.1	MANE Select	c.187T>A	p.Cys63Ser	missense	Exon 3 of 9	ENSP00000509569.1	A0A494C1S0
	SPDYE1	ENST00000258704.3	TSL:1	c.67T>A	p.Cys23Ser	missense	Exon 1 of 7	ENSP00000258704.3	Q8NFV5
	POLR2J4	ENST00000427076.5	TSL:1	n.444+12501A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446132 Hom.: 0 Cov.: 34 AF XY: 0.00000139 AC XY: 1 AN XY: 719794

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4714

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111912

Other (OTH) AF: 0.00 AC: 0 AN: 60180

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.4
DANN	Benign	0.68
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.00049	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.23
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.045
Sift	Benign	0.52	T
Sift4G	Benign	0.71	T
Polyphen		0.0050	B
Vest4		0.098
MutPred		0.36		Gain of phosphorylation at C23 (P = 0.0087)
MVP		0.048
MPC		1.7
ClinPred		0.052	T
PromoterAI		0.0063	Neutral
Varity_R		0.11
gMVP		0.023
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs572510223; hg19: chr7-44040691;