6-30654817-C-G

Position:

• chr6-30654817-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003587.5(DHX16):​c.2886G>C​(p.Val962=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,613,036 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (23 hom.)
• Consequence: DHX16 NM_003587.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.679

Genes affected

DHX16 (HGNC:2739): (DEAH-box helicase 16) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is a functional homolog of fission yeast Prp8 protein involved in cell cycle progression. This gene is mapped to the MHC region on chromosome 6p21.3, a region where many malignant, genetic and autoimmune disease genes are linked. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2018]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-30654817-C-G is Benign according to our data. Variant chr6-30654817-C-G is described in ClinVar as [Benign]. Clinvar id is 711864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.679 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00228 (347/152322) while in subpopulation NFE AF= 0.00303 (206/68040). AF 95% confidence interval is 0.00269. There are 1 homozygotes in gnomad4. There are 157 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 347 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHX16	NM_003587.5	c.2886G>C	p.Val962=	synonymous_variant	19/20	ENST00000376442.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHX16	ENST00000376442.8	c.2886G>C	p.Val962=	synonymous_variant	19/20	1	NM_003587.5	P1
DHX16	ENST00000376437.9	c.1443G>C	p.Val481=	synonymous_variant	11/12	1

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 348 AN: 152204 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00346 AC: 852 AN: 245976 Hom.: 6 AF XY: 0.00368 AC XY: 494 AN XY: 134184

Gnomad AFR exome AF: 0.000266

Gnomad AMR exome AF: 0.00386

Gnomad ASJ exome AF: 0.0123

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.00247

Gnomad FIN exome AF: 0.000926

Gnomad NFE exome AF: 0.00426

Gnomad OTH exome AF: 0.00429

GnomAD4 exome AF: 0.00260 AC: 3792 AN: 1460714 Hom.: 23 Cov.: 32 AF XY: 0.00273 AC XY: 1985 AN XY: 726682

Gnomad4 AFR exome AF: 0.000597

Gnomad4 AMR exome AF: 0.00385

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00263

Gnomad4 FIN exome AF: 0.00117

Gnomad4 NFE exome AF: 0.00236

Gnomad4 OTH exome AF: 0.00373

GnomAD4 genome AF: 0.00228 AC: 347 AN: 152322 Hom.: 1 Cov.: 32 AF XY: 0.00211 AC XY: 157 AN XY: 74488

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00303

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00329 Hom.: 0

Bravo AF: 0.00262

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00703

EpiControl AF: 0.00800

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 25, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2022	DHX16: BP4, BP7, BS1, BS2 -

DHX16-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.8
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs146265602; hg19: chr6-30622594;