22-23118816-G-C

Variant names:

• chr22-23118816-G-C
• rs885964
• NM_002073.4:c.724-4271G>C

Variant summary

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

The NM_002073.4(GNAZ):​c.724-4271G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,152 control chromosomes in the GnomAD database, including 18,262 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 0.48 (18262 hom., cov: 34)
• Consequence: GNAZ NM_002073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002073.4. 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.724-4271G>C		intron	N/A	NP_002064.1
	RSPH14	NM_014433.3	MANE Select	c.421+15210C>G		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.724-4271G>C		intron	N/A	ENSP00000478892.1
	RSPH14	ENST00000216036.9	TSL:1 MANE Select	c.421+15210C>G		intron	N/A	ENSP00000216036.4

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72739 AN: 152034 Hom.: 18258 Cov.: 34

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.478 AC: 72772 AN: 152152 Hom.: 18262 Cov.: 34 AF XY: 0.477 AC XY: 35449 AN XY: 74394

African (AFR) AF: 0.325 AC: 13491 AN: 41524

American (AMR) AF: 0.523 AC: 8004 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1873 AN: 3472

East Asian (EAS) AF: 0.391 AC: 2018 AN: 5164

South Asian (SAS) AF: 0.432 AC: 2085 AN: 4822

European-Finnish (FIN) AF: 0.521 AC: 5518 AN: 10594

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38040 AN: 67964

Other (OTH) AF: 0.495 AC: 1046 AN: 2114

Alfa AF: 0.517 Hom.: 2587

Bravo AF: 0.473

Asia WGS AF: 0.411 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.39
PhyloP100		-2.1
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: rs885964; hg19: chr22-23461003;