Variant 7-122076559-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005763.4(AASS):c.2711A>G(p.Tyr904Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000868 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

AASS
NM_005763.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.13

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AASS	NM_005763.4 linkuse as main transcript	c.2711A>G	p.Tyr904Cys	missense_variant	24/24	ENST00000417368.7	NP_005754.2
AASS	XM_011515725.3 linkuse as main transcript	c.2615A>G	p.Tyr872Cys	missense_variant	23/23		XP_011514027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AASS	ENST00000417368.7 linkuse as main transcript	c.2711A>G	p.Tyr904Cys	missense_variant	24/24	1	NM_005763.4	ENSP00000403768	P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250910

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000910

AC:

133

AN:

1461634

Hom.:

Cov.:

AF XY:

0.0000949

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 11, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

T;T

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

.;D

M_CAP

Benign

0.037

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-8.0

D;D

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

1.0

D;D

Vest4

0.90

MVP

0.80

MPC

0.71

ClinPred

0.99

GERP RS

5.7

Varity_R

0.95

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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