rs371422117

Variant names:

• chr19-44172923-C-T
• rs371422117
• NM_001032373.2:c.206C>T

Variant summary

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

The NM_001032373.2(ZNF226):​c.206C>T​(p.Thr69Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000667 in 1,604,454 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 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: ZNF226 NM_001032373.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.466
• Publications: 1 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: 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=0.06064406).

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.206C>T	p.Thr69Met	missense	Exon 5 of 6	NP_001027545.1	Q9NYT6-1
	ZNF226	NM_001032372.2		c.206C>T	p.Thr69Met	missense	Exon 5 of 6	NP_001027544.1	Q9NYT6-1
	ZNF226	NM_001319088.2		c.206C>T	p.Thr69Met	missense	Exon 5 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.206C>T	p.Thr69Met	missense	Exon 5 of 6	ENSP00000336719.5	Q9NYT6-1
	ZNF226	ENST00000454662.6	TSL:1	c.206C>T	p.Thr69Met	missense	Exon 5 of 6	ENSP00000393265.1	Q9NYT6-1
	ZNF226	ENST00000590089.5	TSL:1	c.206C>T	p.Thr69Met	missense	Exon 6 of 7	ENSP00000465121.1	Q9NYT6-1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000860 AC: 20 AN: 232624 AF XY: 0.000104

Gnomad AFR exome AF: 0.000214

Gnomad AMR exome AF: 0.0000919

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000347

GnomAD4 exome AF: 0.0000620 AC: 90 AN: 1452282 Hom.: 0 Cov.: 30 AF XY: 0.0000735 AC XY: 53 AN XY: 721180

African (AFR) AF: 0.000210 AC: 7 AN: 33380

American (AMR) AF: 0.0000923 AC: 4 AN: 43330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25878

East Asian (EAS) AF: 0.00 AC: 0 AN: 39512

South Asian (SAS) AF: 0.00 AC: 0 AN: 83892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000677 AC: 75 AN: 1107366

Other (OTH) AF: 0.0000665 AC: 4 AN: 60132

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74332

African (AFR) AF: 0.000145 AC: 6 AN: 41434

American (AMR) AF: 0.000196 AC: 3 AN: 15270

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

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.000166

ESP6500AA AF: 0.000267 AC: 1

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000994 AC: 12

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	0.082
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.65
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.47
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.024
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.026	D
Polyphen		0.73	P
Vest4		0.084
MVP		0.24
MPC		0.024
ClinPred		0.023	T
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.053
Mutation Taster		=97/3	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: rs371422117; hg19: chr19-44677076; COSMIC: COSV56195889; COSMIC: COSV56195889;