Variant 15-34860074-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_014691.3(AQR):c.4111C>T(p.His1371Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000285 in 1,492,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

AQR
NM_014691.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.70

Variant links:

Genes affected

AQR (HGNC:29513): (aquarius intron-binding spliceosomal factor) Enables 3'-5' RNA helicase activity and single-stranded RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U2-type catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

AQR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, AQR

BP4

Computational evidence support a benign effect (MetaRNN=0.21951625).

BS2

High AC in GnomAd at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQR	NM_014691.3 linkuse as main transcript	c.4111C>T	p.His1371Tyr	missense_variant	34/35	ENST00000156471.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
AQR	ENST00000156471.10 linkuse as main transcript	c.4111C>T	p.His1371Tyr	missense_variant	34/35	1	NM_014691.3	P1
AQR	ENST00000559090.5 linkuse as main transcript	n.2998C>T		non_coding_transcript_exon_variant	3/4	1
AQR	ENST00000559767.1 linkuse as main transcript	n.440C>T		non_coding_transcript_exon_variant	2/3	2
AQR	ENST00000543879.6 linkuse as main transcript	c.*2873C>T		3_prime_UTR_variant, NMD_transcript_variant	33/34	2

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000140

AC:

AN:

221380

Hom.:

AF XY:

0.000165

AC XY:

AN XY:

121058

show subpopulations

Gnomad AFR exome

AF:

0.0000738

Gnomad AMR exome

AF:

0.0000365

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:

0.000268

Gnomad OTH exome

AF:

0.000197

GnomAD4 exome

AF:

0.000297

AC:

398

AN:

1339858

Hom.:

Cov.:

AF XY:

0.000305

AC XY:

201

AN XY:

659052

show subpopulations

Gnomad4 AFR exome

AF:

0.0000328

Gnomad4 AMR exome

AF:

0.0000530

Gnomad4 ASJ exome

AF:

0.0000427

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000409

Gnomad4 NFE exome

AF:

0.000368

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

AF:

0.000177

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000382

Hom.:

Bravo

AF:

0.000196

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000492

AC:

ExAC

AF:

0.000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.4111C>T (p.H1371Y) alteration is located in exon 34 (coding exon 34) of the AQR gene. This alteration results from a C to T substitution at nucleotide position 4111, causing the histidine (H) at amino acid position 1371 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.11

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.018

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.1

Sift

Uncertain

0.013

Sift4G

Uncertain

0.031

Polyphen

0.068

Vest4

0.52

MVP

0.34

MPC

0.088

ClinPred

0.11

GERP RS

5.7

Varity_R

0.35

gMVP

0.42

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