NM_001032373.2:c.553A>G

Variant names:

• chr19-44175815-A-G
• rs1031912005
• NM_001032373.2:c.553A>G

Variant summary

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

The NM_001032373.2(ZNF226):​c.553A>G​(p.Asn185Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,446 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF226 NM_001032373.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780
• Publications: 0 publications found

Genes affected

ZNF226 (HGNC:13019): (zinc finger protein 226) 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: 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=0.078983605).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032373.2. 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
	ZNF226	NM_001032373.2	MANE Select	c.553A>G	p.Asn185Asp	missense	Exon 6 of 6	NP_001027545.1	Q9NYT6-1
	ZNF226	NM_001032372.2		c.553A>G	p.Asn185Asp	missense	Exon 6 of 6	NP_001027544.1	Q9NYT6-1
	ZNF226	NM_001319088.2		c.553A>G	p.Asn185Asp	missense	Exon 6 of 6	NP_001306017.1	Q9NYT6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF226	ENST00000337433.10	TSL:1 MANE Select	c.553A>G	p.Asn185Asp	missense	Exon 6 of 6	ENSP00000336719.5	Q9NYT6-1
	ZNF226	ENST00000454662.6	TSL:1	c.553A>G	p.Asn185Asp	missense	Exon 6 of 6	ENSP00000393265.1	Q9NYT6-1
	ZNF226	ENST00000590089.5	TSL:1	c.553A>G	p.Asn185Asp	missense	Exon 7 of 7	ENSP00000465121.1	Q9NYT6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461446 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726976

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111800

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.070
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.35
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.039	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.078
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.038
Sift	Benign	0.17	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.33		Loss of MoRF binding (P = 0.0425)
MVP		0.32
MPC		0.019
ClinPred		0.029	T
GERP RS		1.5
Varity_R		0.056
gMVP		0.14
Mutation Taster		=99/1	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: rs1031912005; hg19: chr19-44679968;