NM_014003.4:c.69T>C

Variant names:

• chr16-72096226-T-C
• rs11554764
• NM_014003.4:c.69T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014003.4(DHX38):​c.69T>C​(p.Gly23Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 1,614,078 control chromosomes in the GnomAD database, including 2,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (164 hom., cov: 32)
  • Exomes 𝑓: 0.050 (2043 hom.)
• Consequence: DHX38 NM_014003.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.83
• Publications: 18 publications found

Genes affected

DHX38 (HGNC:17211): (DEAH-box helicase 38) 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. The protein encoded by this gene is a member of the DEAD/H box family of splicing factors. This protein resembles yeast Prp16 more closely than other DEAD/H family members. It is an ATPase and essential for the catalytic step II in pre-mRNA splicing process. [provided by RefSeq, Jul 2008]

DHX38 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 84

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-72096226-T-C is Benign according to our data. Variant chr16-72096226-T-C is described in ClinVar as Benign. ClinVar VariationId is 1167323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014003.4. 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
	DHX38	NM_014003.4	MANE Select	c.69T>C	p.Gly23Gly	synonymous	Exon 2 of 27	NP_054722.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX38	ENST00000268482.8	TSL:1 MANE Select	c.69T>C	p.Gly23Gly	synonymous	Exon 2 of 27	ENSP00000268482.3	Q92620-1
	DHX38	ENST00000904787.1		c.69T>C	p.Gly23Gly	synonymous	Exon 2 of 27	ENSP00000574846.1
	DHX38	ENST00000904788.1		c.69T>C	p.Gly23Gly	synonymous	Exon 2 of 27	ENSP00000574847.1

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6742 AN: 152172 Hom.: 157 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.0492

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0532

GnomAD2 exomes AF: 0.0431 AC: 10832 AN: 251146 AF XY: 0.0434

Gnomad AFR exome AF: 0.0312

Gnomad AMR exome AF: 0.0347

Gnomad ASJ exome AF: 0.0344

Gnomad EAS exome AF: 0.0511

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0529

Gnomad OTH exome AF: 0.0401

GnomAD4 exome AF: 0.0502 AC: 73330 AN: 1461788 Hom.: 2043 Cov.: 30 AF XY: 0.0496 AC XY: 36082 AN XY: 727180

African (AFR) AF: 0.0317 AC: 1061 AN: 33480

American (AMR) AF: 0.0343 AC: 1532 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0315 AC: 823 AN: 26136

East Asian (EAS) AF: 0.0497 AC: 1974 AN: 39696

South Asian (SAS) AF: 0.0279 AC: 2406 AN: 86256

European-Finnish (FIN) AF: 0.0344 AC: 1837 AN: 53380

Middle Eastern (MID) AF: 0.0479 AC: 276 AN: 5760

European-Non Finnish (NFE) AF: 0.0544 AC: 60490 AN: 1111966

Other (OTH) AF: 0.0485 AC: 2931 AN: 60394

GnomAD4 genome AF: 0.0445 AC: 6774 AN: 152290 Hom.: 164 Cov.: 32 AF XY: 0.0433 AC XY: 3228 AN XY: 74464

African (AFR) AF: 0.0323 AC: 1342 AN: 41572

American (AMR) AF: 0.0387 AC: 592 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3470

East Asian (EAS) AF: 0.0493 AC: 255 AN: 5170

South Asian (SAS) AF: 0.0294 AC: 142 AN: 4828

European-Finnish (FIN) AF: 0.0300 AC: 319 AN: 10616

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0566 AC: 3852 AN: 68012

Other (OTH) AF: 0.0531 AC: 112 AN: 2110

Alfa AF: 0.0527 Hom.: 401

Bravo AF: 0.0445

Asia WGS AF: 0.0560 AC: 195 AN: 3478

EpiCase AF: 0.0538

EpiControl AF: 0.0542

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.50
PhyloP100		-2.8
Mutation Taster		=98/2	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: rs11554764; hg19: chr16-72130125; COSMIC: COSV51699950; COSMIC: COSV51699950;