chr22-23124893-C-T

Variant names:

• chr22-23124893-C-T
• rs13407
• NM_002073.4:c.*1462C>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.*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
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 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.*1462C>T		3_prime_UTR	Exon 3 of 3	NP_002064.1
	RSPH14	NM_014433.3	MANE Select	c.421+9133G>A		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.*1462C>T		3_prime_UTR	Exon 3 of 3	ENSP00000478892.1
	RSPH14	ENST00000216036.9	TSL:1 MANE Select	c.421+9133G>A		intron	N/A	ENSP00000216036.4
	RSPH14	ENST00000421213.1	TSL:3	c.50-393G>A		intron	N/A	ENSP00000414155.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 10 AN: 20

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.500 AC: 14 AN: 28

European-Finnish (FIN) AF: 0.511 AC: 91 AN: 178

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.559 AC: 132 AN: 236

Other (OTH) AF: 0.750 AC: 6 AN: 8

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

African (AFR) AF: 0.351 AC: 14569 AN: 41480

American (AMR) AF: 0.527 AC: 8061 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1855 AN: 3470

East Asian (EAS) AF: 0.393 AC: 2035 AN: 5176

South Asian (SAS) AF: 0.437 AC: 2109 AN: 4824

European-Finnish (FIN) AF: 0.513 AC: 5428 AN: 10580

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37953 AN: 67978

Other (OTH) AF: 0.495 AC: 1046 AN: 2112

Alfa AF: 0.523 Hom.: 5694

Bravo AF: 0.481

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-0.55
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: rs13407; hg19: chr22-23467080; COSMIC: COSV50739998; COSMIC: COSV50739998;