chr22-23122623-G-A

Variant names:

• chr22-23122623-G-A
• rs4820537
• ENST00000479571.1:n.246G>A

Variant summary

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

The ENST00000479571.1(GNAZ):​n.246G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 168,026 control chromosomes in the GnomAD database, including 14,753 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 0.40 (13132 hom., cov: 32)
  • Exomes 𝑓: 0.43 (1621 hom.)
• Consequence: GNAZ ENST00000479571.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 11 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000479571.1. 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.724-464G>A		intron	N/A	NP_002064.1
	RSPH14	NM_014433.3	MANE Select	c.421+11403C>T		intron	N/A	NP_055248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAZ	ENST00000479571.1	TSL:1	n.246G>A		non_coding_transcript_exon	Exon 1 of 2
	GNAZ	ENST00000615612.2	TSL:1 MANE Select	c.724-464G>A		intron	N/A	ENSP00000478892.1
	RSPH14	ENST00000216036.9	TSL:1 MANE Select	c.421+11403C>T		intron	N/A	ENSP00000216036.4

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60755 AN: 151986 Hom.: 13135 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.432 AC: 6878 AN: 15922 Hom.: 1621 Cov.: 0 AF XY: 0.429 AC XY: 3594 AN XY: 8368

African (AFR) AF: 0.191 AC: 108 AN: 566

American (AMR) AF: 0.474 AC: 1341 AN: 2832

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 112 AN: 298

East Asian (EAS) AF: 0.339 AC: 395 AN: 1164

South Asian (SAS) AF: 0.363 AC: 551 AN: 1518

European-Finnish (FIN) AF: 0.413 AC: 104 AN: 252

Middle Eastern (MID) AF: 0.467 AC: 14 AN: 30

European-Non Finnish (NFE) AF: 0.464 AC: 3977 AN: 8564

Other (OTH) AF: 0.395 AC: 276 AN: 698

GnomAD4 genome AF: 0.400 AC: 60779 AN: 152104 Hom.: 13132 Cov.: 32 AF XY: 0.399 AC XY: 29662 AN XY: 74348

African (AFR) AF: 0.223 AC: 9264 AN: 41514

American (AMR) AF: 0.460 AC: 7034 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1402 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1925 AN: 5172

South Asian (SAS) AF: 0.399 AC: 1922 AN: 4822

European-Finnish (FIN) AF: 0.444 AC: 4697 AN: 10574

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33016 AN: 67942

Other (OTH) AF: 0.419 AC: 886 AN: 2114

Alfa AF: 0.468 Hom.: 26602

Bravo AF: 0.395

Asia WGS AF: 0.381 AC: 1326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.18
DANN	Benign	0.75
PhyloP100		0.44
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: rs4820537; hg19: chr22-23464810;