22-23109049-G-T

Variant names:

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

Variant summary

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

The NM_002073.4(GNAZ):​c.723+12631G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,242 control chromosomes in the GnomAD database, including 2,620 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 0.10 (2620 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAZ	NM_002073.4	c.723+12631G>T		intron_variant	Intron 2 of 2	ENST00000615612.2	NP_002064.1
RSPH14	NM_014433.3	c.421+24977C>A		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>T		intron_variant	Intron 2 of 2	1	NM_002073.4	ENSP00000478892.1
RSPH14	ENST00000216036.9	c.421+24977C>A		intron_variant	Intron 4 of 6	1	NM_014433.3	ENSP00000216036.4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15779 AN: 152124 Hom.: 2615 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0388

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.00442

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00595

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.104 AC: 15823 AN: 152242 Hom.: 2620 Cov.: 33 AF XY: 0.101 AC XY: 7483 AN XY: 74452

African (AFR) AF: 0.349 AC: 14480 AN: 41484

American (AMR) AF: 0.0388 AC: 594 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 82 AN: 3472

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5178

South Asian (SAS) AF: 0.00890 AC: 43 AN: 4830

European-Finnish (FIN) AF: 0.00442 AC: 47 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00595 AC: 405 AN: 68018

Other (OTH) AF: 0.0667 AC: 141 AN: 2114

Alfa AF: 0.0457 Hom.: 2277

Bravo AF: 0.119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.031
DANN	Benign	0.80
PhyloP100		-1.0
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: rs16997431; hg19: chr22-23451236;