rs5759593

Positions:

• chr22-23122270-A-G
• chr22-23122270-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002073.4(GNAZ):​c.724-817A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,164 control chromosomes in the GnomAD database, including 20,586 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 0.50 (20572 hom., cov: 32)
  • Exomes 𝑓: 0.54 (14 hom.)
• Consequence: GNAZ NM_002073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

Genes affected

GNAZ (HGNC:4395): (G protein subunit alpha z) The protein encoded by this gene is a member of a G protein subfamily that mediates signal transduction in pertussis toxin-insensitive systms. This encoded protein may play a role in maintaining the ionic balance of perilymphatic and endolymphatic cochlear fluids. [provided by RefSeq, Jul 2008]

RSPH14 (HGNC:13437): (radial spoke head 14 homolog) This gene encodes a protein with no known function but with slight similarity to a yeast vacuolar protein. The gene is located in a region deleted in pediatric rhabdoid tumors of the brain, kidney and soft tissues, but mutations in this gene have not been associated with the disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAZ	NM_002073.4	c.724-817A>G		intron_variant		ENST00000615612.2
RSPH14	NM_014433.3	c.421+11756T>C		intron_variant		ENST00000216036.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH14	ENST00000216036.9	c.421+11756T>C		intron_variant		1	NM_014433.3	P1
GNAZ	ENST00000615612.2	c.724-817A>G		intron_variant		1	NM_002073.4	P1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76695 AN: 151962 Hom.: 20572 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.536 AC: 45 AN: 84 Hom.: 14 AF XY: 0.485 AC XY: 33 AN XY: 68

Gnomad4 AFR exome AF: 0.750

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.505 AC: 76727 AN: 152080 Hom.: 20572 Cov.: 32 AF XY: 0.501 AC XY: 37284 AN XY: 74350

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.520

Alfa AF: 0.573 Hom.: 5173

Bravo AF: 0.497

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.18

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: rs5759593; hg19: chr22-23464457;