20-33732015-C-T

Variant names:

• chr20-33732015-C-T
• rs536226894
• NM_001282933.2:c.-7C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001282933.2(ZNF341):​c.-7C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000487 in 1,425,798 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00023 (4 hom.)
• Consequence: ZNF341 NM_001282933.2 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.40
• Publications: 0 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000229188 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 20-33732015-C-T is Benign according to our data. Variant chr20-33732015-C-T is described in ClinVar as Benign. ClinVar VariationId is 3042456.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0026 (395/151780) while in subpopulation AFR AF = 0.00891 (369/41422). AF 95% confidence interval is 0.00816. There are 3 homozygotes in GnomAd4. There are 200 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF341	NM_001282933.2	MANE Select	c.-7C>T		5_prime_UTR	Exon 1 of 15	NP_001269862.1	Q9BYN7-1
	ZNF341	NM_032819.5		c.-7C>T		5_prime_UTR	Exon 1 of 15	NP_116208.3
	ZNF341	NM_001282935.2		c.-80C>T		5_prime_UTR	Exon 1 of 14	NP_001269864.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF341	ENST00000375200.6	TSL:1 MANE Select	c.-7C>T		5_prime_UTR	Exon 1 of 15	ENSP00000364346.1	Q9BYN7-1
	ZNF341	ENST00000342427.6	TSL:1	c.-7C>T		5_prime_UTR	Exon 1 of 15	ENSP00000344308.2	Q9BYN7-2
	ZNF341	ENST00000483118.5	TSL:1	n.-7C>T		non_coding_transcript_exon	Exon 1 of 14	ENSP00000432933.1	E9PN62

Frequencies

GnomAD3 genomes AF: 0.00260 AC: 394 AN: 151666 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00891

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000961

GnomAD2 exomes AF: 0.000370 AC: 23 AN: 62180 AF XY: 0.000283

Gnomad AFR exome AF: 0.0120

Gnomad AMR exome AF: 0.000656

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000235 AC: 299 AN: 1274018 Hom.: 4 Cov.: 30 AF XY: 0.000227 AC XY: 142 AN XY: 626414

African (AFR) AF: 0.0101 AC: 254 AN: 25188

American (AMR) AF: 0.000305 AC: 6 AN: 19672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21050

East Asian (EAS) AF: 0.00 AC: 0 AN: 27722

South Asian (SAS) AF: 0.0000449 AC: 3 AN: 66790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41254

Middle Eastern (MID) AF: 0.000228 AC: 1 AN: 4386

European-Non Finnish (NFE) AF: 0.00000197 AC: 2 AN: 1016656

Other (OTH) AF: 0.000643 AC: 33 AN: 51300

GnomAD4 genome AF: 0.00260 AC: 395 AN: 151780 Hom.: 3 Cov.: 31 AF XY: 0.00270 AC XY: 200 AN XY: 74184

African (AFR) AF: 0.00891 AC: 369 AN: 41422

American (AMR) AF: 0.00157 AC: 24 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67862

Other (OTH) AF: 0.000951 AC: 2 AN: 2104

Alfa AF: 0.00167 Hom.: 1

Bravo AF: 0.00287

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ZNF341-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.98
PhyloP100		1.4
PromoterAI		0.0029	Neutral
Mutation Taster		=300/0	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: rs536226894; hg19: chr20-32319821;