rs6546909

Variant names:

• chr2-74519195-A-C
• rs6546909
• NM_133637.3:c.1842T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-74519195-A-C
• chr2-74519195-A-G
• chr2-74519195-A-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_133637.3(DQX1):​c.1842T>G​(p.Leu614Leu) variant causes a synonymous change involving the alteration of a non-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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DQX1 NM_133637.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 37 publications found

Genes affected

DQX1 (HGNC:20410): (DEAQ-box RNA dependent ATPase 1) Predicted to enable RNA binding activity. Predicted to be involved in DNA duplex unwinding. Predicted to be part of spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-0.192 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DQX1	NM_133637.3	c.1842T>G	p.Leu614Leu	synonymous_variant	Exon 11 of 12	ENST00000404568.4	NP_598376.2
DQX1	XM_047443583.1	c.1488T>G	p.Leu496Leu	synonymous_variant	Exon 10 of 11		XP_047299539.1
DQX1	XM_011532645.1	c.1116T>G	p.Leu372Leu	synonymous_variant	Exon 8 of 9		XP_011530947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DQX1	ENST00000404568.4	c.1842T>G	p.Leu614Leu	synonymous_variant	Exon 11 of 12	5	NM_133637.3	ENSP00000384621.3
DQX1	ENST00000393951.6	c.1842T>G	p.Leu614Leu	synonymous_variant	Exon 11 of 12	2		ENSP00000377523.2
DQX1	ENST00000418139.5	n.*662T>G		non_coding_transcript_exon_variant	Exon 8 of 9	5		ENSP00000389196.1
DQX1	ENST00000418139.5	n.*662T>G		3_prime_UTR_variant	Exon 8 of 9	5		ENSP00000389196.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1441724 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 715382

African (AFR) AF: 0.00 AC: 0 AN: 32572

American (AMR) AF: 0.00 AC: 0 AN: 40944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25430

East Asian (EAS) AF: 0.00 AC: 0 AN: 39318

South Asian (SAS) AF: 0.00 AC: 0 AN: 83622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101576

Other (OTH) AF: 0.00 AC: 0 AN: 59456

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.7
DANN	Benign	0.57
PhyloP100		-0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs6546909; hg19: chr2-74746322;