1-200644482-T-C

Variant names:

• chr1-200644482-T-C
• rs114747202
• NM_001031725.6:c.1632A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_001031725.6(DDX59):​c.1632A>G​(p.Thr544Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000472 in 1,597,848 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: DDX59 NM_001031725.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.875
• Publications: 1 publications found

Genes affected

DDX59 (HGNC:25360): (DEAD-box helicase 59) Predicted to enable RNA binding activity and RNA helicase activity. Predicted to be located in cytoplasm and nucleus. Predicted to be integral component of membrane. Implicated in orofaciodigital syndrome V. [provided by Alliance of Genome Resources, Apr 2022]

DDX59 Gene-Disease associations (from GenCC):

• orofaciodigital syndrome V

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.044).
• BP6: Variant 1-200644482-T-C is Benign according to our data. Variant chr1-200644482-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1575037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.875 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000696 (106/152374) while in subpopulation AMR AF = 0.00196 (30/15298). AF 95% confidence interval is 0.00141. There are 0 homozygotes in GnomAd4. There are 50 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031725.6. 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
	DDX59	NM_001031725.6	MANE Select	c.1632A>G	p.Thr544Thr	synonymous	Exon 8 of 8	NP_001026895.2	Q5T1V6-1
	DDX59	NM_001349799.3		c.1632A>G	p.Thr544Thr	synonymous	Exon 8 of 8	NP_001336728.1	Q5T1V6-1
	DDX59	NM_001349800.3		c.1632A>G	p.Thr544Thr	synonymous	Exon 8 of 8	NP_001336729.1	Q5T1V6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX59	ENST00000331314.11	TSL:1 MANE Select	c.1632A>G	p.Thr544Thr	synonymous	Exon 8 of 8	ENSP00000330460.6	Q5T1V6-1
	DDX59	ENST00000936161.1		c.1632A>G	p.Thr544Thr	synonymous	Exon 7 of 7	ENSP00000606220.1
	DDX59	ENST00000936162.1		c.1632A>G	p.Thr544Thr	synonymous	Exon 8 of 8	ENSP00000606221.1

Frequencies

GnomAD3 genomes AF: 0.000696 AC: 106 AN: 152256 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000705

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000591 AC: 140 AN: 236808 AF XY: 0.000601

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000163

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00243

Gnomad NFE exome AF: 0.000713

Gnomad OTH exome AF: 0.000709

GnomAD4 exome AF: 0.000448 AC: 648 AN: 1445474 Hom.: 0 Cov.: 31 AF XY: 0.000476 AC XY: 342 AN XY: 718690

African (AFR) AF: 0.000122 AC: 4 AN: 32728

American (AMR) AF: 0.000307 AC: 13 AN: 42382

Ashkenazi Jewish (ASJ) AF: 0.0000389 AC: 1 AN: 25700

East Asian (EAS) AF: 0.00 AC: 0 AN: 38714

South Asian (SAS) AF: 0.00 AC: 0 AN: 83278

European-Finnish (FIN) AF: 0.00213 AC: 113 AN: 53110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.000443 AC: 489 AN: 1104212

Other (OTH) AF: 0.000470 AC: 28 AN: 59632

GnomAD4 genome AF: 0.000696 AC: 106 AN: 152374 Hom.: 0 Cov.: 32 AF XY: 0.000671 AC XY: 50 AN XY: 74516

African (AFR) AF: 0.000120 AC: 5 AN: 41592

American (AMR) AF: 0.00196 AC: 30 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10630

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

European-Non Finnish (NFE) AF: 0.000705 AC: 48 AN: 68038

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000795 Hom.: 0

Bravo AF: 0.00103

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.46
PhyloP100		-0.88
Mutation Taster		=100/0	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: rs114747202; hg19: chr1-200613610;