7-44002800-C-G

Variant names:

• chr7-44002800-C-G
• rs764948935
• NM_001378423.2:c.590C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001378423.2(SPDYE1):​c.590C>G​(p.Ala197Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 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. A197V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 15)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDYE1 NM_001378423.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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:56874):

ENSG00000273432 (HGNC:):

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26348025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPDYE1	NM_001378423.2	c.590C>G	p.Ala197Gly	missense_variant	Exon 4 of 9	ENST00000693451.1	NP_001365352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPDYE1	ENST00000693451.1	c.590C>G	p.Ala197Gly	missense_variant	Exon 4 of 9		NM_001378423.2	ENSP00000509569.1

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD3 exomes AF: 0.0000101 AC: 2 AN: 198846 Hom.: 0 AF XY: 0.00000921 AC XY: 1 AN XY: 108560

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 SAS exome AF: 0.0000724

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: 0.00000141 AC: 2 AN: 1414806 Hom.: 0 Cov.: 28 AF XY: 0.00000142 AC XY: 1 AN XY: 702660

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000239

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 15

ExAC AF: 0.00000847 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.00073	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.097
Sift	Benign	0.048	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.96	D
Vest4		0.17
MutPred		0.39		Loss of stability (P = 0.0831);
MVP		0.20
MPC		1.4
ClinPred		0.36	T
Varity_R		0.12
gMVP		0.086

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

Publications

LitVar

Other links and lift over

dbSNP: rs764948935; hg19: chr7-44042399;