22-23116390-G-A

Variant names:

• chr22-23116390-G-A
• rs13054985
• NM_002073.4:c.724-6697G>A

Variant summary

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

The ENST00000615612.2(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 ENST00000615612.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615612.2. 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
	GNAZ	NM_002073.4	MANE Select	c.724-6697G>A		intron	N/A	NP_002064.1
	RSPH14	NM_014433.3	MANE Select	c.421+17636C>T		intron	N/A	NP_055248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAZ	ENST00000615612.2	TSL:1 MANE Select	c.724-6697G>A		intron	N/A	ENSP00000478892.1
	RSPH14	ENST00000216036.9	TSL:1 MANE Select	c.421+17636C>T		intron	N/A	ENSP00000216036.4

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

African (AFR) AF: 0.291 AC: 12074 AN: 41546

American (AMR) AF: 0.518 AC: 7927 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1844 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1999 AN: 5174

South Asian (SAS) AF: 0.425 AC: 2054 AN: 4828

European-Finnish (FIN) AF: 0.517 AC: 5481 AN: 10610

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37798 AN: 67998

Other (OTH) AF: 0.482 AC: 1018 AN: 2112

Alfa AF: 0.527 Hom.: 26529

Bravo AF: 0.459

Asia WGS AF: 0.400 AC: 1393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.61
PhyloP100		0.63
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: rs13054985; hg19: chr22-23458577; COSMIC: COSV50740305;