10-37952139-A-C

Variant names:

• chr10-37952139-A-C
• rs1208606
• NM_145011.4:c.1359T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145011.4(ZNF25):​c.1359T>G​(p.Asn453Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 1,562,488 control chromosomes in the GnomAD database, including 4,950 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.060 (352 hom., cov: 33)
  • Exomes 𝑓: 0.076 (4598 hom.)
• Consequence: ZNF25 NM_145011.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 23 publications found

Genes affected

ZNF25 (HGNC:13043): (zinc finger protein 25) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018883944).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF25	NM_145011.4	c.1359T>G	p.Asn453Lys	missense_variant	Exon 6 of 6	ENST00000302609.8	NP_659448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF25	ENST00000302609.8	c.1359T>G	p.Asn453Lys	missense_variant	Exon 6 of 6	1	NM_145011.4	ENSP00000302222.7
ZNF25	ENST00000374633.5	n.1589T>G		non_coding_transcript_exon_variant	Exon 7 of 7	1

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9127 AN: 152160 Hom.: 351 Cov.: 33

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00829

Gnomad FIN AF: 0.0666

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.0717

GnomAD2 exomes AF: 0.0600 AC: 12624 AN: 210314 AF XY: 0.0620

Gnomad AFR exome AF: 0.0147

Gnomad AMR exome AF: 0.0492

Gnomad ASJ exome AF: 0.0843

Gnomad EAS exome AF: 0.0000593

Gnomad FIN exome AF: 0.0716

Gnomad NFE exome AF: 0.0861

Gnomad OTH exome AF: 0.0742

GnomAD4 exome AF: 0.0763 AC: 107644 AN: 1410210 Hom.: 4598 Cov.: 31 AF XY: 0.0748 AC XY: 52114 AN XY: 697124

African (AFR) AF: 0.0140 AC: 437 AN: 31248

American (AMR) AF: 0.0515 AC: 1773 AN: 34414

Ashkenazi Jewish (ASJ) AF: 0.0825 AC: 1883 AN: 22820

East Asian (EAS) AF: 0.0000510 AC: 2 AN: 39186

South Asian (SAS) AF: 0.0126 AC: 985 AN: 78104

European-Finnish (FIN) AF: 0.0709 AC: 3681 AN: 51892

Middle Eastern (MID) AF: 0.0745 AC: 410 AN: 5500

European-Non Finnish (NFE) AF: 0.0865 AC: 94224 AN: 1089030

Other (OTH) AF: 0.0732 AC: 4249 AN: 58016

GnomAD4 genome AF: 0.0599 AC: 9129 AN: 152278 Hom.: 352 Cov.: 33 AF XY: 0.0570 AC XY: 4247 AN XY: 74446

African (AFR) AF: 0.0168 AC: 697 AN: 41566

American (AMR) AF: 0.0644 AC: 986 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3470

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

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4824

European-Finnish (FIN) AF: 0.0666 AC: 706 AN: 10598

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0896 AC: 6096 AN: 68014

Other (OTH) AF: 0.0710 AC: 150 AN: 2114

Alfa AF: 0.0793 Hom.: 1739

Bravo AF: 0.0590

TwinsUK AF: 0.0831 AC: 308

ALSPAC AF: 0.0825 AC: 318

ESP6500AA AF: 0.0182 AC: 80

ESP6500EA AF: 0.0880 AC: 757

ExAC AF: 0.0567 AC: 6878

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.21
DANN	Benign	0.64
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.10	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.18	N
PhyloP100		-0.14
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.072
Sift	Benign	0.15	T
Sift4G	Uncertain	0.044	D
Polyphen		0.0	B
Vest4		0.027
MutPred		0.24		Gain of methylation at N453 (P = 1e-04);
MPC		0.051
ClinPred		0.00058	T
GERP RS		-0.70
Varity_R		0.043
gMVP		0.018
Mutation Taster		=100/0	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: rs1208606; hg19: chr10-38241067; COSMIC: COSV56924019; COSMIC: COSV56924019;