15-34862877-G-C

Variant names:

• chr15-34862877-G-C
• rs1595779493
• NM_014691.3:c.4019C>G
• AQR p.Thr1340Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014691.3(AQR):​c.4019C>G​(p.Thr1340Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1340A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AQR NM_014691.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.00
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17106959).

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.4019C>G	p.Thr1340Ser	missense	Exon 33 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.4019C>G	p.Thr1340Ser	missense	Exon 33 of 35	ENSP00000156471.5	O60306
	AQR	ENST00000559090.5	TSL:1	n.2906C>G		non_coding_transcript_exon	Exon 2 of 4
	AQR	ENST00000875393.1		c.3983C>G	p.Thr1328Ser	missense	Exon 32 of 34	ENSP00000545452.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.084	T
Eigen	Benign	0.040
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.17	T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	0.97	L
PhyloP100		8.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.36
Sift	Benign	0.43	T
Sift4G	Benign	0.45	T
Varity_R		0.17
gMVP		0.31

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1595779493; hg19: chr15-35155078;