Genetic Variant GNAZ:c.*1462C>T (chr22-23124893-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.547

Publications

3 publications found

Variant links:

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]

GNAZ links:

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]

RSPH14 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAZ	NM_002073.4 link	c.*1462C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000615612.2	NP_002064.1
RSPH14	NM_014433.3 link	c.421+9133G>A		intron_variant	Intron 4 of 6	ENST00000216036.9	NP_055248.1	Q9UHP6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GNAZ	ENST00000615612.2 link	c.*1462C>T	3_prime_UTR_variant	Exon 3 of 3	1	NM_002073.4	ENSP00000478892.1	P19086
RSPH14	ENST00000216036.9 link	c.421+9133G>A	intron_variant	Intron 4 of 6	1	NM_014433.3	ENSP00000216036.4	Q9UHP6
RSPH14	ENST00000421213.1 link	c.50-393G>A	intron_variant	Intron 1 of 1	3		ENSP00000414155.1	H7C3W6

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73722

AN:

152016

Hom.:

18525

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.531

AC XY:

152

AN XY:

286

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.511

AC:

AN:

178

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.559

AC:

132

AN:

236

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.485

AC:

73753

AN:

152134

Hom.:

18524

Cov.:

AF XY:

0.482

AC XY:

35885

AN XY:

74386

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1922

3843

5765

7686

9608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

(source)

DANN

Benign

0.69

PhyloP100

-0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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22-23124893-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over