6-30660305-A-G

Variant names:

• chr6-30660305-A-G
• rs3130000
• NM_003587.5:c.1545-63T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003587.5(DHX16):​c.1545-63T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 1,340,388 control chromosomes in the GnomAD database, including 571,334 homozygotes. 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: 𝑓 0.94 (67708 hom., cov: 31)
  • Exomes 𝑓: 0.92 (503626 hom.)
• Consequence: DHX16 NM_003587.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 21 publications found

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]

DHX16 Gene-Disease associations (from GenCC):

• neuromuscular disease and ocular or auditory anomalies with or without seizures

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003587.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX16	NM_003587.5	MANE Select	c.1545-63T>C		intron	N/A	NP_003578.2
	DHX16	NM_001164239.2		c.1365-63T>C		intron	N/A	NP_001157711.1
	DHX16	NM_001363515.2		c.102-63T>C		intron	N/A	NP_001350444.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX16	ENST00000376442.8	TSL:1 MANE Select	c.1545-63T>C		intron	N/A	ENSP00000365625.3
	DHX16	ENST00000376437.9	TSL:1	c.102-63T>C		intron	N/A	ENSP00000365620.5
	DHX16	ENST00000480966.1	TSL:2	n.273T>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143356 AN: 152144 Hom.: 67651 Cov.: 31

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.948

GnomAD4 exome AF: 0.920 AC: 1093415 AN: 1188126 Hom.: 503626 Cov.: 15 AF XY: 0.922 AC XY: 538842 AN XY: 584408

African (AFR) AF: 0.987 AC: 25963 AN: 26292

American (AMR) AF: 0.964 AC: 23047 AN: 23908

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 17155 AN: 17916

East Asian (EAS) AF: 0.998 AC: 35385 AN: 35464

South Asian (SAS) AF: 0.982 AC: 56788 AN: 57844

European-Finnish (FIN) AF: 0.914 AC: 41349 AN: 45230

Middle Eastern (MID) AF: 0.950 AC: 4643 AN: 4888

European-Non Finnish (NFE) AF: 0.909 AC: 842910 AN: 926892

Other (OTH) AF: 0.929 AC: 46175 AN: 49692

GnomAD4 genome AF: 0.942 AC: 143472 AN: 152262 Hom.: 67708 Cov.: 31 AF XY: 0.943 AC XY: 70160 AN XY: 74428

African (AFR) AF: 0.986 AC: 40957 AN: 41558

American (AMR) AF: 0.952 AC: 14548 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3320 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5159 AN: 5178

South Asian (SAS) AF: 0.983 AC: 4744 AN: 4826

European-Finnish (FIN) AF: 0.916 AC: 9706 AN: 10600

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61875 AN: 68026

Other (OTH) AF: 0.949 AC: 2008 AN: 2116

Alfa AF: 0.921 Hom.: 105890

Bravo AF: 0.948

Asia WGS AF: 0.984 AC: 3424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.8
DANN	Benign	0.75
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs3130000; hg19: chr6-30628082;