chr22-23096349-C-T

Variant names:

• chr22-23096349-C-T
• rs2230332
• NM_002073.4:c.654C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002073.4(GNAZ):​c.654C>T​(p.Gly218Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,502 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (6 hom.)
• Consequence: GNAZ NM_002073.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00700
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 22-23096349-C-T is Benign according to our data. Variant chr22-23096349-C-T is described in ClinVar as Benign. ClinVar VariationId is 720633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.007 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00563 (858/152292) while in subpopulation AFR AF = 0.0198 (821/41562). AF 95% confidence interval is 0.0186. There are 3 homozygotes in GnomAd4. There are 430 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 858 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAZ	NM_002073.4	MANE Select	c.654C>T	p.Gly218Gly	synonymous	Exon 2 of 3	NP_002064.1	P19086
	RSPH14	NM_014433.3	MANE Select	c.422-32216G>A		intron	N/A	NP_055248.1	Q9UHP6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAZ	ENST00000615612.2	TSL:1 MANE Select	c.654C>T	p.Gly218Gly	synonymous	Exon 2 of 3	ENSP00000478892.1	P19086
	RSPH14	ENST00000216036.9	TSL:1 MANE Select	c.422-32216G>A		intron	N/A	ENSP00000216036.4	Q9UHP6
	GNAZ	ENST00000956660.1		c.654C>T	p.Gly218Gly	synonymous	Exon 3 of 4	ENSP00000626719.1

Frequencies

GnomAD3 genomes AF: 0.00562 AC: 855 AN: 152174 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00148 AC: 371 AN: 250966 AF XY: 0.00102

Gnomad AFR exome AF: 0.0201

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00103

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000560 AC: 819 AN: 1461210 Hom.: 6 Cov.: 33 AF XY: 0.000451 AC XY: 328 AN XY: 726888

African (AFR) AF: 0.0207 AC: 692 AN: 33474

American (AMR) AF: 0.000693 AC: 31 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52898

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5766

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111880

Other (OTH) AF: 0.000778 AC: 47 AN: 60386

GnomAD4 genome AF: 0.00563 AC: 858 AN: 152292 Hom.: 3 Cov.: 33 AF XY: 0.00577 AC XY: 430 AN XY: 74468

African (AFR) AF: 0.0198 AC: 821 AN: 41562

American (AMR) AF: 0.00150 AC: 23 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00264 Hom.: 5

Bravo AF: 0.00641

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.7
DANN	Benign	0.81
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism

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: rs2230332; hg19: chr22-23438536;