20-33788939-C-T

Variant names:

• chr20-33788939-C-T
• rs140105337
• NM_001282933.2:c.1929C>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.1929C>T​(p.Ile643Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,614,028 control chromosomes in the GnomAD database, including 475 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (31 hom., cov: 32)
  • Exomes 𝑓: 0.024 (444 hom.)
• Consequence: ZNF341 NM_001282933.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.60
• Publications: 5 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=-0.24).
• BP6: Variant 20-33788939-C-T is Benign according to our data. Variant chr20-33788939-C-T is described in ClinVar as [Benign]. Clinvar id is 1170037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.6 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0161 (2459/152288) while in subpopulation NFE AF = 0.0255 (1735/68026). AF 95% confidence interval is 0.0245. There are 31 homozygotes in GnomAd4. There are 1144 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF341	NM_001282933.2	c.1929C>T	p.Ile643Ile	synonymous_variant	Exon 13 of 15	ENST00000375200.6	NP_001269862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF341	ENST00000375200.6	c.1929C>T	p.Ile643Ile	synonymous_variant	Exon 13 of 15	1	NM_001282933.2	ENSP00000364346.1

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2457 AN: 152170 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.00393

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0210

GnomAD2 exomes AF: 0.0182 AC: 4582 AN: 251326 AF XY: 0.0184

Gnomad AFR exome AF: 0.00455

Gnomad AMR exome AF: 0.0119

Gnomad ASJ exome AF: 0.0167

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0172

Gnomad NFE exome AF: 0.0282

Gnomad OTH exome AF: 0.0209

GnomAD4 exome AF: 0.0239 AC: 34872 AN: 1461740 Hom.: 444 Cov.: 31 AF XY: 0.0234 AC XY: 16991 AN XY: 727162

African (AFR) AF: 0.00358 AC: 120 AN: 33480

American (AMR) AF: 0.0126 AC: 565 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 453 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00781 AC: 674 AN: 86252

European-Finnish (FIN) AF: 0.0187 AC: 998 AN: 53338

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5768

European-Non Finnish (NFE) AF: 0.0278 AC: 30894 AN: 1111962

Other (OTH) AF: 0.0187 AC: 1128 AN: 60390

GnomAD4 genome AF: 0.0161 AC: 2459 AN: 152288 Hom.: 31 Cov.: 32 AF XY: 0.0154 AC XY: 1144 AN XY: 74462

African (AFR) AF: 0.00392 AC: 163 AN: 41560

American (AMR) AF: 0.0132 AC: 202 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4824

European-Finnish (FIN) AF: 0.0156 AC: 166 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1735 AN: 68026

Other (OTH) AF: 0.0208 AC: 44 AN: 2114

Alfa AF: 0.0218 Hom.: 28

Bravo AF: 0.0163

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0237

EpiControl AF: 0.0261

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ZNF341-related disorder Benign:1

Mar 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	10
DANN	Benign	0.91
PhyloP100		2.6
Mutation Taster		=96/4	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: rs140105337; hg19: chr20-32376745;