rs12217

Variant names:

• chr7-122074599-C-T
• rs12217
• NM_005763.4:c.*1890G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005763.4(AASS):​c.*1890G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,080 control chromosomes in the GnomAD database, including 32,239 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (32239 hom., cov: 32)
• Consequence: AASS NM_005763.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791
• Publications: 3 publications found

Genes affected

AASS (HGNC:17366): (aminoadipate-semialdehyde synthase) This gene encodes a bifunctional enzyme that catalyzes the first two steps in the mammalian lysine degradation pathway. The N-terminal and the C-terminal portions of this enzyme contain lysine-ketoglutarate reductase and saccharopine dehydrogenase activity, respectively, resulting in the conversion of lysine to alpha-aminoadipic semialdehyde. Mutations in this gene are associated with familial hyperlysinemia. [provided by RefSeq, Jul 2008]

AASS Gene-Disease associations (from GenCC):

• hyperlysinemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AASS	NM_005763.4	c.*1890G>A		3_prime_UTR_variant	Exon 24 of 24	ENST00000417368.7	NP_005754.2
AASS	XM_011515725.3	c.*1890G>A		3_prime_UTR_variant	Exon 23 of 23		XP_011514027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AASS	ENST00000417368.7	c.*1890G>A		3_prime_UTR_variant	Exon 24 of 24	1	NM_005763.4	ENSP00000403768.2

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95865 AN: 151962 Hom.: 32160 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.631 AC: 96006 AN: 152080 Hom.: 32239 Cov.: 32 AF XY: 0.626 AC XY: 46554 AN XY: 74324

African (AFR) AF: 0.887 AC: 36826 AN: 41528

American (AMR) AF: 0.541 AC: 8275 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1853 AN: 3472

East Asian (EAS) AF: 0.600 AC: 3090 AN: 5154

South Asian (SAS) AF: 0.583 AC: 2813 AN: 4822

European-Finnish (FIN) AF: 0.475 AC: 4999 AN: 10518

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36357 AN: 67984

Other (OTH) AF: 0.588 AC: 1243 AN: 2114

Alfa AF: 0.549 Hom.: 36630

Bravo AF: 0.643

Asia WGS AF: 0.587 AC: 2039 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.40
PhyloP100		-0.79

Splicing

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

Other links and lift over

dbSNP: rs12217; hg19: chr7-121714653;