19-44130883-C-T

Variant names:

• chr19-44130883-C-T
• rs888944504
• NM_013362.4:c.269C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013362.4(ZNF225):​c.269C>T​(p.Ser90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,170 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 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ZNF225 NM_013362.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.67
• Publications: 0 publications found

Genes affected

ZNF225 (HGNC:13018): (zinc finger protein 225) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04292631).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013362.4. 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
	ZNF225	NM_013362.4	MANE Select	c.269C>T	p.Ser90Leu	missense	Exon 5 of 5	NP_037494.2	Q9UK10
	ZNF225	NM_001321685.2		c.269C>T	p.Ser90Leu	missense	Exon 6 of 6	NP_001308614.1	Q9UK10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF225	ENST00000262894.11	TSL:1 MANE Select	c.269C>T	p.Ser90Leu	missense	Exon 5 of 5	ENSP00000262894.5	Q9UK10
	ZNF225	ENST00000590612.1	TSL:1	c.269C>T	p.Ser90Leu	missense	Exon 4 of 4	ENSP00000468686.1	Q9UK10
	ZNF225	ENST00000860840.1		c.269C>T	p.Ser90Leu	missense	Exon 6 of 6	ENSP00000530899.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461120 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 726840

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111650

Other (OTH) AF: 0.0000166 AC: 1 AN: 60358

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152050 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74246

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.098
DANN	Benign	0.29
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.00039	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PhyloP100		-3.7
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.014
Sift	Benign	0.39	T
Sift4G	Benign	0.28	T
Polyphen		0.049	B
Vest4		0.030
MutPred		0.28		Loss of phosphorylation at S90 (P = 0.0352)
MVP		0.048
MPC		0.097
ClinPred		0.046	T
GERP RS		-4.6
Varity_R		0.017
gMVP		0.010
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs888944504; hg19: chr19-44635036;