16-3137597-G-A

Variant names:

• chr16-3137597-G-A
• rs747985785
• NM_004220.3:c.317G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004220.3(ZNF213):​c.317G>A​(p.Arg106His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R106C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: ZNF213 NM_004220.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.718
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08507416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF213	NM_004220.3	c.317G>A	p.Arg106His	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.317G>A	p.Arg106His	missense_variant	Exon 2 of 6	1	NM_004220.3	ENSP00000380087.3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 250772 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461708 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12 AN XY: 727164

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53250

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74356

African (AFR) AF: 0.0000965 AC: 4 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4836

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000762 Hom.: 0

Bravo AF: 0.0000416

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.317G>A (p.R106H) 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 317, causing the arginine (R) at amino acid position 106 to be replaced by a histidine (H). 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	0.27
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.19	T;T;T;T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.66	.;.;.;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.085	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M;M;M;M;.
PhyloP100		-0.72
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.1	.;D;.;.;.
REVEL	Benign	0.089
Sift	Uncertain	0.0090	.;D;.;.;.
Sift4G	Uncertain	0.042	D;D;D;D;T
Polyphen		0.037	B;B;B;B;.
Vest4		0.21
MVP		0.13
MPC		0.26
ClinPred		0.17	T
GERP RS		-1.6
PromoterAI		-0.027	Neutral
Varity_R		0.082
gMVP		0.20
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747985785; hg19: chr16-3187598;