chr22-41325849-C-T

Variant names:

• chr22-41325849-C-T
• rs151077891
• NM_017590.6:c.216C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_017590.6(ZC3H7B):​c.216C>T​(p.Asp72Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,612,670 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (48 hom.)
• Consequence: ZC3H7B NM_017590.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.452
• Publications: 0 publications found

Genes affected

ZC3H7B (HGNC:30869): (zinc finger CCCH-type containing 7B) This gene encodes a protein that contains a tetratricopeptide repeat domain. The encoded protein also interacts with the rotavirus non-structural protein NSP3. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 22-41325849-C-T is Benign according to our data. Variant chr22-41325849-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2653226.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.452 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00484 (7064/1460322) while in subpopulation MID AF = 0.0333 (171/5128). AF 95% confidence interval is 0.0293. There are 48 homozygotes in GnomAdExome4. There are 3559 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 642 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017590.6. 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
	ZC3H7B	NM_017590.6	MANE Select	c.216C>T	p.Asp72Asp	synonymous	Exon 4 of 23	NP_060060.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H7B	ENST00000352645.5	TSL:1 MANE Select	c.216C>T	p.Asp72Asp	synonymous	Exon 4 of 23	ENSP00000345793.4	Q9UGR2
	ZC3H7B	ENST00000897616.1		c.216C>T	p.Asp72Asp	synonymous	Exon 4 of 23	ENSP00000567675.1
	ZC3H7B	ENST00000897617.1		c.216C>T	p.Asp72Asp	synonymous	Exon 4 of 22	ENSP00000567676.1

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 645 AN: 152230 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00988

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00488

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00494 AC: 1232 AN: 249350 AF XY: 0.00507

Gnomad AFR exome AF: 0.000871

Gnomad AMR exome AF: 0.00440

Gnomad ASJ exome AF: 0.0112

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0104

Gnomad NFE exome AF: 0.00544

Gnomad OTH exome AF: 0.00737

GnomAD4 exome AF: 0.00484 AC: 7064 AN: 1460322 Hom.: 48 Cov.: 32 AF XY: 0.00490 AC XY: 3559 AN XY: 726402

African (AFR) AF: 0.00185 AC: 62 AN: 33444

American (AMR) AF: 0.00455 AC: 203 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.0122 AC: 319 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00222 AC: 191 AN: 86000

European-Finnish (FIN) AF: 0.00822 AC: 439 AN: 53380

Middle Eastern (MID) AF: 0.0333 AC: 171 AN: 5128

European-Non Finnish (NFE) AF: 0.00479 AC: 5328 AN: 1111716

Other (OTH) AF: 0.00582 AC: 351 AN: 60290

GnomAD4 genome AF: 0.00421 AC: 642 AN: 152348 Hom.: 4 Cov.: 32 AF XY: 0.00426 AC XY: 317 AN XY: 74496

African (AFR) AF: 0.000986 AC: 41 AN: 41574

American (AMR) AF: 0.00536 AC: 82 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4830

European-Finnish (FIN) AF: 0.00988 AC: 105 AN: 10626

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00488 AC: 332 AN: 68034

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00496 Hom.: 2

Bravo AF: 0.00390

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00731

EpiControl AF: 0.00744

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs151077891; hg19: chr22-41721853;