20-33788942-C-T

Variant names:

• chr20-33788942-C-T
• rs34260449
• NM_001282933.2:c.1932C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001282933.2(ZNF341):​c.1932C>T​(p.His644His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,613,978 control chromosomes in the GnomAD database, including 375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (31 hom., cov: 32)
  • Exomes 𝑓: 0.020 (344 hom.)
• Consequence: ZNF341 NM_001282933.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.255
• Publications: 4 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-AS1 (HGNC:50736): (ZNF341 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 20-33788942-C-T is Benign according to our data. Variant chr20-33788942-C-T is described in ClinVar as Benign. ClinVar VariationId is 1169237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.255 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0152 (2314/152260) while in subpopulation NFE AF = 0.0231 (1573/68020). AF 95% confidence interval is 0.0222. There are 31 homozygotes in GnomAd4. There are 1114 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 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.1932C>T	p.His644His	synonymous	Exon 13 of 15	NP_001269862.1	Q9BYN7-1
	ZNF341	NM_032819.5		c.1911C>T	p.His637His	synonymous	Exon 13 of 15	NP_116208.3
	ZNF341	NM_001282935.2		c.1662C>T	p.His554His	synonymous	Exon 12 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.1932C>T	p.His644His	synonymous	Exon 13 of 15	ENSP00000364346.1	Q9BYN7-1
	ZNF341	ENST00000342427.6	TSL:1	c.1911C>T	p.His637His	synonymous	Exon 13 of 15	ENSP00000344308.2	Q9BYN7-2
	ZNF341	ENST00000483118.5	TSL:1	n.*20C>T		non_coding_transcript_exon	Exon 12 of 14	ENSP00000432933.1	E9PN62

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2316 AN: 152142 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.00840

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0215

GnomAD2 exomes AF: 0.0168 AC: 4216 AN: 251300 AF XY: 0.0183

Gnomad AFR exome AF: 0.00252

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00822

Gnomad NFE exome AF: 0.0234

Gnomad OTH exome AF: 0.0187

GnomAD4 exome AF: 0.0199 AC: 29092 AN: 1461718 Hom.: 344 Cov.: 31 AF XY: 0.0201 AC XY: 14591 AN XY: 727142

African (AFR) AF: 0.00349 AC: 117 AN: 33478

American (AMR) AF: 0.0131 AC: 585 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0103 AC: 270 AN: 26134

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

South Asian (SAS) AF: 0.0220 AC: 1901 AN: 86258

European-Finnish (FIN) AF: 0.00769 AC: 410 AN: 53326

Middle Eastern (MID) AF: 0.0366 AC: 211 AN: 5766

European-Non Finnish (NFE) AF: 0.0221 AC: 24533 AN: 1111944

Other (OTH) AF: 0.0176 AC: 1063 AN: 60394

GnomAD4 genome AF: 0.0152 AC: 2314 AN: 152260 Hom.: 31 Cov.: 32 AF XY: 0.0150 AC XY: 1114 AN XY: 74432

African (AFR) AF: 0.00325 AC: 135 AN: 41554

American (AMR) AF: 0.0211 AC: 323 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0203 AC: 98 AN: 4826

European-Finnish (FIN) AF: 0.00840 AC: 89 AN: 10594

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0231 AC: 1573 AN: 68020

Other (OTH) AF: 0.0208 AC: 44 AN: 2116

Alfa AF: 0.0198 Hom.: 64

Bravo AF: 0.0153

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.0251

EpiControl AF: 0.0236

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ZNF341-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	7.5
DANN	Benign	0.90
PhyloP100		-0.26
Mutation Taster		=99/1	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: rs34260449; hg19: chr20-32376748;