rs13054985

chr22-23116390-G-Achr22-23116390-G-C

Variant summary

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

The NM_002073.4(GNAZ):c.724-6697G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,248 control chromosomes in the GnomAD database, including 17,593 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 0.47 (17593 hom., cov: 35)
• Consequence: GNAZ NM_002073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAZ	NM_002073.4	c.724-6697G>A		intron_variant		ENST00000615612.2
RSPH14	NM_014433.3	c.421+17636C>T		intron_variant		ENST00000216036.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH14	ENST00000216036.9	c.421+17636C>T		intron_variant		1	NM_014433.3	P1
GNAZ	ENST00000615612.2	c.724-6697G>A		intron_variant		1	NM_002073.4	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70871 AN: 152128 Hom.: 17595 Cov.: 35

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.484

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.466 AC: 70892 AN: 152248 Hom.: 17593 Cov.: 35 AF XY: 0.464 AC XY: 34521 AN XY: 74430

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.482

Alfa AF: 0.537 Hom.: 20516

Bravo AF: 0.459

Asia WGS AF: 0.400 AC: 1393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.6
Dann	Benign	0.61

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: rs13054985; hg19: chr22-23458577; COSMIC: COSV50740305;