20-33745375-G-T

Variant names:

• chr20-33745375-G-T
• rs7274811
• NM_001282933.2:c.339+76G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001282933.2(ZNF341):​c.339+76G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,438,444 control chromosomes in the GnomAD database, including 45,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4406 hom., cov: 32)
  • Exomes 𝑓: 0.25 (41154 hom.)
• Consequence: ZNF341 NM_001282933.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.338
• Publications: 68 publications found

Genes affected

ZNF341 (HGNC:15992): (zinc finger protein 341) Enables DNA binding activity and DNA-binding transcription activator activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in nucleus. Implicated in hyper IgE recurrent infection syndrome 3. [provided by Alliance of Genome Resources, Apr 2022]

ZNF341 Gene-Disease associations (from GenCC):

• hyper-IgE recurrent infection syndrome 3, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 20-33745375-G-T is Benign according to our data. Variant chr20-33745375-G-T is described in ClinVar as Benign. ClinVar VariationId is 2628155.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282933.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF341	NM_001282933.2	MANE Select	c.339+76G>T		intron	N/A	NP_001269862.1
	ZNF341	NM_032819.5		c.339+76G>T		intron	N/A	NP_116208.3
	ZNF341	NM_001282935.2		c.70-3548G>T		intron	N/A	NP_001269864.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF341	ENST00000375200.6	TSL:1 MANE Select	c.339+76G>T		intron	N/A	ENSP00000364346.1
	ZNF341	ENST00000342427.6	TSL:1	c.339+76G>T		intron	N/A	ENSP00000344308.2
	ZNF341	ENST00000483118.5	TSL:1	n.339+76G>T		intron	N/A	ENSP00000432933.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35686 AN: 151988 Hom.: 4403 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.249 AC: 320005 AN: 1286338 Hom.: 41154 AF XY: 0.247 AC XY: 155889 AN XY: 632396

African (AFR) AF: 0.196 AC: 5837 AN: 29726

American (AMR) AF: 0.390 AC: 12918 AN: 33130

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 4422 AN: 21658

East Asian (EAS) AF: 0.221 AC: 7876 AN: 35646

South Asian (SAS) AF: 0.194 AC: 14016 AN: 72422

European-Finnish (FIN) AF: 0.230 AC: 8993 AN: 39124

Middle Eastern (MID) AF: 0.218 AC: 1152 AN: 5280

European-Non Finnish (NFE) AF: 0.253 AC: 251311 AN: 995096

Other (OTH) AF: 0.248 AC: 13480 AN: 54256

GnomAD4 genome AF: 0.235 AC: 35712 AN: 152106 Hom.: 4406 Cov.: 32 AF XY: 0.235 AC XY: 17474 AN XY: 74364

African (AFR) AF: 0.194 AC: 8051 AN: 41498

American (AMR) AF: 0.315 AC: 4814 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1242 AN: 5166

South Asian (SAS) AF: 0.190 AC: 916 AN: 4830

European-Finnish (FIN) AF: 0.239 AC: 2529 AN: 10580

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.245 AC: 16653 AN: 67990

Other (OTH) AF: 0.227 AC: 478 AN: 2108

Alfa AF: 0.242 Hom.: 20143

Bravo AF: 0.243

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 55% of patients studied by a panel of primary immunodeficiencies. Number of patients: 53. Only high quality variants are reported.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.90
DANN	Benign	0.49
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs7274811; hg19: chr20-32333181;