15-34856907-G-A

Variant names:

• chr15-34856907-G-A
• rs184384582
• NM_014691.3:c.4343C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014691.3(AQR):​c.4343C>T​(p.Pro1448Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000816 in 1,614,094 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00085 (2 hom.)
• Consequence: AQR NM_014691.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017267913).
• BS2: High AC in GnomAd4 at 74 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014691.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQR	NM_014691.3	MANE Select	c.4343C>T	p.Pro1448Leu	missense	Exon 35 of 35	NP_055506.1	O60306

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQR	ENST00000156471.10	TSL:1 MANE Select	c.4343C>T	p.Pro1448Leu	missense	Exon 35 of 35	ENSP00000156471.5	O60306
	AQR	ENST00000559090.5	TSL:1	n.3230C>T		non_coding_transcript_exon	Exon 4 of 4
	AQR	ENST00000875393.1		c.4307C>T	p.Pro1436Leu	missense	Exon 34 of 34	ENSP00000545452.1

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152120 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000489 AC: 122 AN: 249322 AF XY: 0.000518

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.000902

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000850 AC: 1243 AN: 1461856 Hom.: 2 Cov.: 40 AF XY: 0.000799 AC XY: 581 AN XY: 727230

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86244

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00104 AC: 1161 AN: 1111996

Other (OTH) AF: 0.000927 AC: 56 AN: 60394

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152238 Hom.: 1 Cov.: 31 AF XY: 0.000376 AC XY: 28 AN XY: 74448

African (AFR) AF: 0.000241 AC: 10 AN: 41532

American (AMR) AF: 0.000196 AC: 3 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000760 Hom.: 1

Bravo AF: 0.000555

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00107 AC: 9

ExAC AF: 0.000471 AC: 57

EpiCase AF: 0.000709

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Benign	0.61
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.90	N
Sift	Benign	0.22	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.17
MVP		0.34
MPC		0.061
ClinPred		0.0075	T
GERP RS		4.1
Varity_R		0.017
gMVP		0.18
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs184384582; hg19: chr15-35149108;