rs74882337

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_005763.4(AASS):c.1678C>T(p.Pro560Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00606 in 1,613,710 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 37 hom. )

Consequence

AASS
NM_005763.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: 7.69

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-122093136-G-A is Benign according to our data. Variant chr7-122093136-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 377290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-122093136-G-A is described in Lovd as [Likely_benign]. Variant chr7-122093136-G-A is described in Lovd as [Pathogenic].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00449 (683/152236) while in subpopulation NFE AF= 0.00785 (534/68022). AF 95% confidence interval is 0.0073. There are 3 homozygotes in gnomad4. There are 312 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AASS	NM_005763.4 link	c.1678C>T	p.Pro560Ser	missense_variant	Exon 16 of 24	ENST00000417368.7	NP_005754.2	Q9UDR5A4D0W4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AASS	ENST00000417368.7 link	c.1678C>T	p.Pro560Ser	missense_variant	Exon 16 of 24	1	NM_005763.4	ENSP00000403768.2		Q9UDR5

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

683

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00785

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00384

AC:

964

AN:

250956

Hom.:

AF XY:

0.00364

AC XY:

493

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00814

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00268

Gnomad NFE exome

AF:

0.00690

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00623

AC:

9098

AN:

1461474

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

4355

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00792

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00316

Gnomad4 NFE exome

AF:

0.00759

Gnomad4 OTH exome

AF:

0.00396

GnomAD4 genome

AF:

0.00449

AC:

683

AN:

152236

Hom.:

Cov.:

AF XY:

0.00419

AC XY:

312

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00785

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00638

Hom.:

Bravo

AF:

0.00448

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00390

AC:

473

EpiCase

AF:

0.00562

EpiControl

AF:

0.00557

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:4

Nov 07, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 08, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AASS: BS2 -

AASS-related disorder

Benign:1

May 09, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hyperlysinemia

Benign:1

Oct 20, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.96

.;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.22

Sift

Benign

0.74

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.95

P;P

Vest4

0.68

MVP

0.72

MPC

0.63

ClinPred

0.026

GERP RS

6.0

Varity_R

0.26

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: -15

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over