8-122951840-C-T

Variant names:

• chr8-122951840-C-T
• rs73335724
• NM_014943.5:c.330C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014943.5(ZHX2):​c.330C>T​(p.Tyr110Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 1,614,128 control chromosomes in the GnomAD database, including 320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (152 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (168 hom.)
• Consequence: ZHX2 NM_014943.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.413
• Publications: 4 publications found

Genes affected

ZHX2 (HGNC:18513): (zinc fingers and homeoboxes 2) The members of the zinc fingers and homeoboxes gene family are nuclear homodimeric transcriptional repressors that interact with the A subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. This gene encodes member 2 of this gene family. In addition to forming homodimers, this protein heterodimerizes with member 1 of the zinc fingers and homeoboxes family. [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=-0.48).
• BP6: Variant 8-122951840-C-T is Benign according to our data. Variant chr8-122951840-C-T is described in ClinVar as Benign. ClinVar VariationId is 783532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.413 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014943.5. 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
	ZHX2	NM_014943.5	MANE Select	c.330C>T	p.Tyr110Tyr	synonymous	Exon 3 of 4	NP_055758.1	Q9Y6X8
	ZHX2	NM_001362797.2		c.330C>T	p.Tyr110Tyr	synonymous	Exon 4 of 5	NP_001349726.1	Q9Y6X8
	ZHX2	NM_001412796.1		c.330C>T	p.Tyr110Tyr	synonymous	Exon 4 of 5	NP_001399725.1	Q9Y6X8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZHX2	ENST00000314393.6	TSL:1 MANE Select	c.330C>T	p.Tyr110Tyr	synonymous	Exon 3 of 4	ENSP00000314709.4	Q9Y6X8
	ZHX2	ENST00000892386.1		c.330C>T	p.Tyr110Tyr	synonymous	Exon 4 of 5	ENSP00000562445.1
	ZHX2	ENST00000892387.1		c.330C>T	p.Tyr110Tyr	synonymous	Exon 4 of 5	ENSP00000562446.1

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3867 AN: 152128 Hom.: 149 Cov.: 31

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0215

GnomAD2 exomes AF: 0.00672 AC: 1689 AN: 251390 AF XY: 0.00496

Gnomad AFR exome AF: 0.0913

Gnomad AMR exome AF: 0.00402

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00274 AC: 4001 AN: 1461882 Hom.: 168 Cov.: 31 AF XY: 0.00245 AC XY: 1781 AN XY: 727244

African (AFR) AF: 0.0939 AC: 3144 AN: 33480

American (AMR) AF: 0.00499 AC: 223 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86258

European-Finnish (FIN) AF: 0.000243 AC: 13 AN: 53410

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.000168 AC: 187 AN: 1112010

Other (OTH) AF: 0.00637 AC: 385 AN: 60396

GnomAD4 genome AF: 0.0256 AC: 3891 AN: 152246 Hom.: 152 Cov.: 31 AF XY: 0.0246 AC XY: 1831 AN XY: 74434

African (AFR) AF: 0.0883 AC: 3667 AN: 41518

American (AMR) AF: 0.0100 AC: 153 AN: 15300

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68022

Other (OTH) AF: 0.0213 AC: 45 AN: 2114

Alfa AF: 0.00884 Hom.: 43

Bravo AF: 0.0301

Asia WGS AF: 0.00635 AC: 23 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000178

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	-0.48
CADD	Benign	5.8
DANN	Benign	0.67
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73335724; hg19: chr8-123964080;