rs9749449

Variant names:

• chr19-57633347-A-G
• rs9749449
• NM_006385.5:c.1A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PVS1_Supporting BA1

The NM_006385.5(ZNF211):​c.1A>G​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,585,452 control chromosomes in the GnomAD database, including 21,282 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2663 hom., cov: 32)
  • Exomes 𝑓: 0.16 (18619 hom.)
• Consequence: ZNF211 NM_006385.5 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812
• Publications: 18 publications found

Genes affected

ZNF211 (HGNC:13003): (zinc finger protein 211) This gene encodes a protein containing a Kruppel-associated box domain and multiple zinc finger domains. This protein may play a role in developmental processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 21 codons. Genomic position: 57633407. Lost 0.035 part of the original CDS.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF211	NM_006385.5	c.1A>G	p.Met1?	start_lost	Exon 1 of 4	ENST00000240731.5	NP_006376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF211	ENST00000240731.5	c.1A>G	p.Met1?	start_lost	Exon 1 of 4	2	NM_006385.5	ENSP00000240731.4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27410 AN: 151910 Hom.: 2655 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.197

GnomAD2 exomes AF: 0.172 AC: 34059 AN: 198158 AF XY: 0.173

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.335

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.157 AC: 225717 AN: 1433424 Hom.: 18619 Cov.: 32 AF XY: 0.159 AC XY: 112910 AN XY: 710802

African (AFR) AF: 0.221 AC: 7318 AN: 33160

American (AMR) AF: 0.140 AC: 5763 AN: 41054

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 5478 AN: 25398

East Asian (EAS) AF: 0.297 AC: 11504 AN: 38770

South Asian (SAS) AF: 0.197 AC: 16217 AN: 82478

European-Finnish (FIN) AF: 0.131 AC: 6075 AN: 46314

Middle Eastern (MID) AF: 0.228 AC: 1234 AN: 5424

European-Non Finnish (NFE) AF: 0.147 AC: 161852 AN: 1101488

Other (OTH) AF: 0.173 AC: 10276 AN: 59338

GnomAD4 genome AF: 0.181 AC: 27464 AN: 152028 Hom.: 2663 Cov.: 32 AF XY: 0.181 AC XY: 13418 AN XY: 74326

African (AFR) AF: 0.224 AC: 9267 AN: 41462

American (AMR) AF: 0.167 AC: 2553 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 748 AN: 3468

East Asian (EAS) AF: 0.321 AC: 1645 AN: 5118

South Asian (SAS) AF: 0.198 AC: 957 AN: 4822

European-Finnish (FIN) AF: 0.142 AC: 1509 AN: 10590

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10167 AN: 67964

Other (OTH) AF: 0.200 AC: 422 AN: 2112

Alfa AF: 0.169 Hom.: 1211

Bravo AF: 0.186

TwinsUK AF: 0.147 AC: 545

ALSPAC AF: 0.139 AC: 535

ESP6500AA AF: 0.186 AC: 795

ESP6500EA AF: 0.140 AC: 1174

ExAC AF: 0.157 AC: 18603

Asia WGS AF: 0.252 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.0
DANN	Benign	0.61
DEOGEN2	Benign	0.00093	.;T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Uncertain	0.90	D;D;D;D
MetaRNN	Benign	0.0041	T;T;T;T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.81
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.064
Sift	Pathogenic	0.0	D;T;T;T
Sift4G	Benign	0.81	T;T;.;.
Polyphen		0.0	.;B;.;.
Vest4		0.078
ClinPred		0.017	T
GERP RS		-0.42
PromoterAI		0.14	Neutral
Varity_R		0.098
gMVP		0.32
Mutation Taster		=194/6	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: rs9749449; hg19: chr19-58144715; COSMIC: COSV53742795;