rs3363

Variant names:

• chr20-45948675-C-G
• rs3363
• NM_022095.4:c.*278G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-45948675-C-G
• chr20-45948675-C-T

Variant summary

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

The NM_022095.4(ZNF335):​c.*278G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 449,044 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00043 (0 hom.)
• Consequence: ZNF335 NM_022095.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.441
• Publications: 17 publications found

Genes affected

ZNF335 (HGNC:15807): (zinc finger protein 335) The protein encoded by this gene enhances transcriptional activation by ligand-bound nuclear hormone receptors. However, it does this not by direct interaction with the receptor, but by direct interaction with the nuclear hormone receptor transcriptional coactivator NRC. The encoded protein may function by altering local chromatin structure. [provided by RefSeq, Jul 2008]

ZNF335 Gene-Disease associations (from GenCC):

• microcephalic primordial dwarfism due to ZNF335 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 20-45948675-C-G is Benign according to our data. Variant chr20-45948675-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1197755.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00308 (469/152198) while in subpopulation AFR AF = 0.0107 (445/41528). AF 95% confidence interval is 0.00989. There are 2 homozygotes in GnomAd4. There are 226 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022095.4. 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
	ZNF335	NM_022095.4	MANE Select	c.*278G>C		3_prime_UTR	Exon 28 of 28	NP_071378.1	Q9H4Z2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF335	ENST00000322927.3	TSL:1 MANE Select	c.*278G>C		3_prime_UTR	Exon 28 of 28	ENSP00000325326.2	Q9H4Z2-1
	ZNF335	ENST00000944756.1		c.*278G>C		3_prime_UTR	Exon 28 of 28	ENSP00000614815.1
	ZNF335	ENST00000862676.1		c.*278G>C		3_prime_UTR	Exon 27 of 27	ENSP00000532735.1

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 469 AN: 152078 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

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: 0.000103

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000431 AC: 128 AN: 296846 Hom.: 0 Cov.: 3 AF XY: 0.000373 AC XY: 59 AN XY: 157972

African (AFR) AF: 0.0101 AC: 87 AN: 8572

American (AMR) AF: 0.000789 AC: 11 AN: 13950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8486

East Asian (EAS) AF: 0.00 AC: 0 AN: 16576

South Asian (SAS) AF: 0.00 AC: 0 AN: 42652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15902

Middle Eastern (MID) AF: 0.000822 AC: 1 AN: 1216

European-Non Finnish (NFE) AF: 0.0000693 AC: 12 AN: 173102

Other (OTH) AF: 0.00104 AC: 17 AN: 16390

GnomAD4 genome AF: 0.00308 AC: 469 AN: 152198 Hom.: 2 Cov.: 33 AF XY: 0.00304 AC XY: 226 AN XY: 74394

African (AFR) AF: 0.0107 AC: 445 AN: 41528

American (AMR) AF: 0.000915 AC: 14 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67994

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00 Hom.: 4047

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.2
DANN	Benign	0.65
PhyloP100		-0.44
Mutation Taster		=100/0	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: rs3363; hg19: chr20-44577314;