dbSNP rs4820537: GNAZ:n.246G>A (chr22-23122623-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000479571.1(GNAZ):n.246G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 168,026 control chromosomes in the GnomAD database, including 14,753 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 0.40 ( 13132 hom., cov: 32)

Exomes 𝑓: 0.43 ( 1621 hom. )

Consequence

GNAZ
ENST00000479571.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.440

Publications

11 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAZ	NM_002073.4 link	c.724-464G>A		intron_variant	Intron 2 of 2	ENST00000615612.2	NP_002064.1
RSPH14	NM_014433.3 link	c.421+11403C>T		intron_variant	Intron 4 of 6	ENST00000216036.9	NP_055248.1	Q9UHP6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GNAZ	ENST00000479571.1 link	n.246G>A	non_coding_transcript_exon_variant	Exon 1 of 2	1
GNAZ	ENST00000615612.2 link	c.724-464G>A	intron_variant	Intron 2 of 2	1	NM_002073.4	ENSP00000478892.1	P19086
RSPH14	ENST00000216036.9 link	c.421+11403C>T	intron_variant	Intron 4 of 6	1	NM_014433.3	ENSP00000216036.4	Q9UHP6

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60755

AN:

151986

Hom.:

13135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.460

Gnomad ASJ

AF:

0.404

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.486

Gnomad OTH

AF:

0.421

GnomAD4 exome

AF:

0.432

AC:

6878

AN:

15922

Hom.:

1621

Cov.:

AF XY:

0.429

AC XY:

3594

AN XY:

8368

show subpopulations

African (AFR)

AF:

0.191

AC:

108

AN:

566

American (AMR)

AF:

0.474

AC:

1341

AN:

2832

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

112

AN:

298

East Asian (EAS)

AF:

0.339

AC:

395

AN:

1164

South Asian (SAS)

AF:

0.363

AC:

551

AN:

1518

European-Finnish (FIN)

AF:

0.413

AC:

104

AN:

252

Middle Eastern (MID)

AF:

0.467

AC:

AN:

European-Non Finnish (NFE)

AF:

0.464

AC:

3977

AN:

8564

Other (OTH)

AF:

0.395

AC:

276

AN:

698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

188

376

563

751

939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.400

AC:

60779

AN:

152104

Hom.:

13132

Cov.:

AF XY:

0.399

AC XY:

29662

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.223

AC:

9264

AN:

41514

American (AMR)

AF:

0.460

AC:

7034

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

1402

AN:

3470

East Asian (EAS)

AF:

0.372

AC:

1925

AN:

5172

South Asian (SAS)

AF:

0.399

AC:

1922

AN:

4822

European-Finnish (FIN)

AF:

0.444

AC:

4697

AN:

10574

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.486

AC:

33016

AN:

67942

Other (OTH)

AF:

0.419

AC:

886

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1829

3658

5488

7317

9146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.468

Hom.:

26602

Bravo

AF:

0.395

Asia WGS

AF:

0.381

AC:

1326

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.18

(source)

DANN

Benign

0.75

PhyloP100

0.44

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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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