22-23109049-G-T

Position:

• chr22-23109049-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GNAZ	NM_002073.4	c.723+12631G>T		intron_variant		ENST00000615612.2	NP_002064.1
RSPH14	NM_014433.3	c.421+24977C>A		intron_variant		ENST00000216036.9	NP_055248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAZ	ENST00000615612.2	c.723+12631G>T		intron_variant		1	NM_002073.4	ENSP00000478892.1
RSPH14	ENST00000216036.9	c.421+24977C>A		intron_variant		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

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.0388

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.00483

Gnomad4 SAS AF: 0.00890

Gnomad4 FIN AF: 0.00442

Gnomad4 NFE AF: 0.00595

Gnomad4 OTH AF: 0.0667

Alfa AF: 0.0175 Hom.: 340

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs16997431; hg19: chr22-23451236;