rs9612234

Positions:

• chr22-23124893-C-T
• chr22-23124893-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002073.4(GNAZ):​c.*1462C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,606 control chromosomes in the GnomAD database, including 18,586 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 (18524 hom., cov: 34)
  • Exomes 𝑓: 0.54 (62 hom.)
• Consequence: GNAZ NM_002073.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAZ	NM_002073.4	c.*1462C>T		3_prime_UTR_variant	3/3	ENST00000615612.2
RSPH14	NM_014433.3	c.421+9133G>A		intron_variant		ENST00000216036.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAZ	ENST00000615612.2	c.*1462C>T		3_prime_UTR_variant	3/3	1	NM_002073.4	P1
RSPH14	ENST00000216036.9	c.421+9133G>A		intron_variant		1	NM_014433.3	P1
RSPH14	ENST00000421213.1	c.50-393G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73722 AN: 152016 Hom.: 18525 Cov.: 34

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.498

GnomAD4 exome AF: 0.538 AC: 254 AN: 472 Hom.: 62 Cov.: 0 AF XY: 0.531 AC XY: 152 AN XY: 286

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.559

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.485 AC: 73753 AN: 152134 Hom.: 18524 Cov.: 34 AF XY: 0.482 AC XY: 35885 AN XY: 74386

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.495

Alfa AF: 0.521 Hom.: 2652

Bravo AF: 0.481

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.69

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: rs13407; hg19: chr22-23467080; COSMIC: COSV50739998; COSMIC: COSV50739998;