rs34332105

Variant names:

• chr19-18920635-C-T
• rs34332105
• NM_019070.5:c.171C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_019070.5(DDX49):​c.171C>T​(p.Val57Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,611,850 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (7 hom.)
• Consequence: DDX49 NM_019070.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0300
• Publications: 1 publications found

Genes affected

DDX49 (HGNC:18684): (DEAD-box helicase 49) Enables RNA binding activity. Involved in positive regulation of cell growth and regulation of rRNA stability. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268193 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 19-18920635-C-T is Benign according to our data. Variant chr19-18920635-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2649602.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.03 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019070.5. 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
	DDX49	NM_019070.5	MANE Select	c.171C>T	p.Val57Val	synonymous	Exon 2 of 13	NP_061943.2
	DDX49	NR_033677.2		n.143-16C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX49	ENST00000247003.9	TSL:1 MANE Select	c.171C>T	p.Val57Val	synonymous	Exon 2 of 13	ENSP00000247003.3	Q9Y6V7-1
	DDX49	ENST00000595858.5	TSL:1	n.171C>T		non_coding_transcript_exon	Exon 2 of 14	ENSP00000471292.1	M0R0K1
	ENSG00000268193	ENST00000596918.5	TSL:5	n.*168-7589G>A		intron	N/A	ENSP00000469669.1	M0R1B8

Frequencies

GnomAD3 genomes AF: 0.00152 AC: 232 AN: 152180 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00203 AC: 509 AN: 251340 AF XY: 0.00201

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00208

Gnomad NFE exome AF: 0.00315

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00229 AC: 3343 AN: 1459552 Hom.: 7 Cov.: 30 AF XY: 0.00228 AC XY: 1653 AN XY: 725528

African (AFR) AF: 0.000359 AC: 12 AN: 33458

American (AMR) AF: 0.000448 AC: 20 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00352 AC: 92 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00157 AC: 135 AN: 86170

European-Finnish (FIN) AF: 0.00279 AC: 149 AN: 53392

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00252 AC: 2797 AN: 1110090

Other (OTH) AF: 0.00227 AC: 137 AN: 60296

GnomAD4 genome AF: 0.00152 AC: 232 AN: 152298 Hom.: 1 Cov.: 32 AF XY: 0.00133 AC XY: 99 AN XY: 74464

African (AFR) AF: 0.000433 AC: 18 AN: 41560

American (AMR) AF: 0.000850 AC: 13 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00251 AC: 171 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00261 Hom.: 2

Bravo AF: 0.00142

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00240

EpiControl AF: 0.00190

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		-0.030
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs34332105; hg19: chr19-19031444; COSMIC: COSV99447387; COSMIC: COSV99447387;