7-44007276-CC-GA

Variant names:

• chr7-44007276-CC-GA
• NM_001378423.2:c.761_762delCCinsGA
• SPDYE1 p.Ala254Gly

Variant summary

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

The NM_001378423.2(SPDYE1):​c.761_762delCCinsGA​(p.Ala254Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPDYE1 NM_001378423.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.983
• 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.

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.761_762delCCinsGA	p.Ala254Gly	missense	N/A	NP_001365352.1	A0A494C1S0
	SPDYE1	NM_175064.4		c.641_642delCCinsGA	p.Ala214Gly	missense	N/A	NP_778234.2
	POLR2J4	NR_003655.3		n.489+6316_489+6317delGGinsTC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDYE1	ENST00000693451.1	MANE Select	c.761_762delCCinsGA	p.Ala254Gly	missense	N/A	ENSP00000509569.1	A0A494C1S0
	SPDYE1	ENST00000258704.3	TSL:1	c.641_642delCCinsGA	p.Ala214Gly	missense	N/A	ENSP00000258704.3	Q8NFV5
	POLR2J4	ENST00000427076.5	TSL:1	n.444+6316_444+6317delGGinsTC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.98

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-44046875;