16-3137675-G-A

Variant names:

• chr16-3137675-G-A
• rs114934528
• NM_004220.3:c.395G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004220.3(ZNF213):​c.395G>A​(p.Arg132Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: ZNF213 NM_004220.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.31
• Publications: 1 publications found

Genes affected

ZNF213 (HGNC:13005): (zinc finger protein 213) C2H2 zinc finger proteins, such as ZNF213, have bipartite structures in which one domain binds DNA or RNA and the other modulates target gene expression.[supplied by OMIM, Apr 2004]

ZNF213-AS1 (HGNC:50505): (ZNF213 antisense RNA 1 (head to head))

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013979167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF213	NM_004220.3	c.395G>A	p.Arg132Gln	missense_variant	Exon 2 of 6	ENST00000396878.8	NP_004211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF213	ENST00000396878.8	c.395G>A	p.Arg132Gln	missense_variant	Exon 2 of 6	1	NM_004220.3	ENSP00000380087.3

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000130 AC: 32 AN: 245840 AF XY: 0.000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00121

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1460948 Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 40 AN XY: 726792

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000448 AC: 2 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.000932 AC: 37 AN: 39682

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52936

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111782

Other (OTH) AF: 0.0000497 AC: 3 AN: 60358

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74472

African (AFR) AF: 0.0000962 AC: 4 AN: 41566

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

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

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5160

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000494 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000989 AC: 12

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.395G>A (p.R132Q) alteration is located in exon 2 (coding exon 1) of the ZNF213 gene. This alteration results from a G to A substitution at nucleotide position 395, causing the arginine (R) at amino acid position 132 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.59
DEOGEN2	Benign	0.018	T;T;T;T;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.14	.;.;.;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.014	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.53	N;N;N;N;.;.
PhyloP100		-1.3
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.91	.;N;.;.;.;.
REVEL	Benign	0.037
Sift	Benign	0.48	.;T;.;.;.;.
Sift4G	Benign	0.58	T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;.;.
Vest4		0.057
MVP		0.10
MPC		0.20
ClinPred		0.0090	T
GERP RS		0.56
PromoterAI		0.0058	Neutral
Varity_R		0.021
gMVP		0.19
Mutation Taster		=298/2	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: rs114934528; hg19: chr16-3187676;