chr22-23109049-G-A

Variant names:

• chr22-23109049-G-A
• rs16997431
• NM_002073.4:c.723+12631G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002073.4(GNAZ):​c.723+12631G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000092 in 152,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000092 (0 hom., cov: 33)
• Consequence: GNAZ NM_002073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 3 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAZ	NM_002073.4	c.723+12631G>A		intron_variant	Intron 2 of 2	ENST00000615612.2	NP_002064.1
RSPH14	NM_014433.3	c.421+24977C>T		intron_variant	Intron 4 of 6	ENST00000216036.9	NP_055248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAZ	ENST00000615612.2	c.723+12631G>A		intron_variant	Intron 2 of 2	1	NM_002073.4	ENSP00000478892.1
RSPH14	ENST00000216036.9	c.421+24977C>T		intron_variant	Intron 4 of 6	1	NM_014433.3	ENSP00000216036.4

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152150 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74338

African (AFR) AF: 0.000193 AC: 8 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 2277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.077
DANN	Benign	0.93
PhyloP100		-1.0

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: rs16997431; hg19: chr22-23451236;