19-11780330-A-G

Variant names:

• chr19-11780330-A-G
• rs144102390
• NM_152355.3:c.506A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_152355.3(ZNF441):​c.506A>G​(p.Tyr169Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000357 in 1,614,216 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (3 hom.)
• Consequence: ZNF441 NM_152355.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.223
• Publications: 4 publications found

Genes affected

ZNF441 (HGNC:20875): (zinc finger protein 441) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005371332).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152355.3. 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
	ZNF441	NM_152355.3	MANE Select	c.506A>G	p.Tyr169Cys	missense	Exon 4 of 4	NP_689568.2	Q8N8Z8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF441	ENST00000357901.5	TSL:3 MANE Select	c.506A>G	p.Tyr169Cys	missense	Exon 4 of 4	ENSP00000350576.4	Q8N8Z8-1
	ZNF441	ENST00000409902.5	TSL:2	n.*435A>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000386658.2	A0A0A0MSF7
	ZNF441	ENST00000409902.5	TSL:2	n.*435A>G		3_prime_UTR	Exon 5 of 5	ENSP00000386658.2	A0A0A0MSF7

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 168 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000653 AC: 164 AN: 251284 AF XY: 0.000619

Gnomad AFR exome AF: 0.00258

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00953

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000280 AC: 409 AN: 1461860 Hom.: 3 Cov.: 34 AF XY: 0.000294 AC XY: 214 AN XY: 727222

African (AFR) AF: 0.00188 AC: 63 AN: 33478

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00846 AC: 221 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53398

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1112010

Other (OTH) AF: 0.000795 AC: 48 AN: 60396

GnomAD4 genome AF: 0.00110 AC: 168 AN: 152356 Hom.: 0 Cov.: 33 AF XY: 0.00109 AC XY: 81 AN XY: 74510

African (AFR) AF: 0.00289 AC: 120 AN: 41582

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000625 Hom.: 2

Bravo AF: 0.000971

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000659 AC: 80

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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	0.13
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.00011	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.22
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.057
Sift	Uncertain	0.019	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.23
MVP		0.65
MPC		1.2
ClinPred		0.072	T
GERP RS		0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.058
Mutation Taster		=100/0	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: rs144102390; hg19: chr19-11891145;