rs12217

Positions:

• chr7-122074599-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
AASS	NM_005763.4	c.*1890G>A		3_prime_UTR_variant	24/24	ENST00000417368.7	NP_005754.2
AASS	XM_011515725.3	c.*1890G>A		3_prime_UTR_variant	23/23		XP_011514027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AASS	ENST00000417368	c.*1890G>A		3_prime_UTR_variant	24/24	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

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.588

Alfa AF: 0.544 Hom.: 30147

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12217; hg19: chr7-121714653;