NM_006869.4:c.727_729delGCAinsTCT

Variant names:

• chr7-900536-TGC-AGA
• NM_006869.4:c.727_729delGCAinsTCT
• ADAP1 p.Ala243Ser

Variant summary

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

The NM_006869.4(ADAP1):​c.727_729delGCAinsTCT​(p.Ala243Ser) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A243T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADAP1 NM_006869.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 0 publications found

Genes affected

ADAP1 (HGNC:16486): (ArfGAP with dual PH domains 1) Enables GTPase activator activity. Involved in regulation of GTPase activity. Located in cytosol; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

COX19 (HGNC:28074): (cytochrome c oxidase assembly factor COX19) COX19 encodes a cytochrome c oxidase (COX)-assembly protein. The S. cerevisiae Cox19 protein may play a role in metal transport to the mitochondrial intermembrane space and assembly of complex IV of the mitochondrial respiratory chain (Sacconi et al., 2005 [PubMed 16212937]).[supplied by OMIM, Mar 2008]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006869.4. 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
	ADAP1	NM_006869.4	MANE Select	c.727_729delGCAinsTCT	p.Ala243Ser	missense	N/A	NP_006860.2	O75689-1
	ADAP1	NM_001284308.2		c.760_762delGCAinsTCT	p.Ala254Ser	missense	N/A	NP_001271237.2	O75689-2
	ADAP1	NM_001284309.2		c.511_513delGCAinsTCT	p.Ala171Ser	missense	N/A	NP_001271238.2	O75689-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAP1	ENST00000265846.10	TSL:1 MANE Select	c.727_729delGCAinsTCT	p.Ala243Ser	missense	N/A	ENSP00000265846.5	O75689-1
	ADAP1	ENST00000539900.5	TSL:2	c.760_762delGCAinsTCT	p.Ala254Ser	missense	N/A	ENSP00000442682.1	O75689-2
	ADAP1	ENST00000943017.1		c.727_729delGCAinsTCT	p.Ala243Ser	missense	N/A	ENSP00000613076.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.12

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: chr7-940173;