chr22-40370354-CAAAAAAA-C

Variant names:

• chr22-40370354-CAAAAAAA-C
• rs11328048
• ENST00000639722.1:n.*1127+3857_*1127+3863delAAAAAAA

Variant summary

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

The NM_001363840.3(ADSL):​c.1431+3871_1431+3877delAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000069 (0 hom., cov: 20)
• Consequence: ADSL NM_001363840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609

Genes affected

ENSG00000284431 (HGNC:):

ADSL (HGNC:291): (adenylosuccinate lyase) The protein encoded by this gene belongs to the lyase 1 family. It is an essential enzyme involved in purine metabolism, and catalyzes two non-sequential reactions in the de novo purine biosynthetic pathway: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and the conversion of adenylosuccinate (S-AMP) to adenosine monophosphate (AMP). Mutations in this gene are associated with adenylosuccinase deficiency (ADSLD), a disorder marked with psychomotor retardation, epilepsy or autistic features. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

SGSM3 (HGNC:25228): (small G protein signaling modulator 3) Enables GTPase activator activity and small GTPase binding activity. Involved in several processes, including Rap protein signal transduction; positive regulation of GTPase activity; and regulation of Rab protein signal transduction. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGSM3	NM_015705.6	c.-445_-439delAAAAAAA		upstream_gene_variant		ENST00000248929.14	NP_056520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284431	ENST00000639722.1	n.*1127+3857_*1127+3863delAAAAAAA		intron_variant	Intron 12 of 30	5		ENSP00000492828.1
SGSM3	ENST00000248929.14	c.-445_-439delAAAAAAA		upstream_gene_variant		1	NM_015705.6	ENSP00000248929.8

Frequencies

GnomAD3 genomes AF: 0.0000695 AC: 6 AN: 86376 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00200

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000846

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

GnomAD4 genome AF: 0.0000694 AC: 6 AN: 86400 Hom.: 0 Cov.: 20 AF XY: 0.0000983 AC XY: 4 AN XY: 40692

African (AFR) AF: 0.00 AC: 0 AN: 22356

American (AMR) AF: 0.00 AC: 0 AN: 9450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2120

East Asian (EAS) AF: 0.00 AC: 0 AN: 2770

South Asian (SAS) AF: 0.00201 AC: 5 AN: 2488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 144

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 41528

Other (OTH) AF: 0.000843 AC: 1 AN: 1186

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11328048; hg19: chr22-40766358;