20-33788858-T-C

Variant names:

• chr20-33788858-T-C
• rs200199641
• NM_001282933.2:c.1853-5T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001282933.2(ZNF341):​c.1853-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,613,306 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (2 hom.)
• Consequence: ZNF341 NM_001282933.2 splice_region, intron
• Scores: Splicing: ADA: 0.01423
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.17
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 20-33788858-T-C is Benign according to our data. Variant chr20-33788858-T-C is described in ClinVar as [Benign]. Clinvar id is 1589300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000348 (53/152324) while in subpopulation EAS AF = 0.00639 (33/5164). AF 95% confidence interval is 0.00468. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF341	NM_001282933.2	c.1853-5T>C		splice_region_variant, intron_variant	Intron 12 of 14	ENST00000375200.6	NP_001269862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF341	ENST00000375200.6	c.1853-5T>C		splice_region_variant, intron_variant	Intron 12 of 14	1	NM_001282933.2	ENSP00000364346.1

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00638

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000543 AC: 136 AN: 250478 AF XY: 0.000509

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00718

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000121 AC: 177 AN: 1460982 Hom.: 2 Cov.: 31 AF XY: 0.000106 AC XY: 77 AN XY: 726826

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00343 AC: 136 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111368

Other (OTH) AF: 0.000646 AC: 39 AN: 60370

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19 AN XY: 74484

African (AFR) AF: 0.00 AC: 0 AN: 41586

American (AMR) AF: 0.00118 AC: 18 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00639 AC: 33 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000427 Hom.: 0

Bravo AF: 0.000363

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.014
dbscSNV1_RF	Benign	0.10
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: rs200199641; hg19: chr20-32376664; COSMIC: COSV107427390;