ENST00000441304.2:c.152T>C

Variant names:

• chr19-12075333-T-C
• rs10424893
• ENST00000441304.2:c.152T>C

Variant summary

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

The ENST00000441304.2(ZNF844):​c.152T>C​(p.Leu51Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,463,466 control chromosomes in the GnomAD database, including 28,569 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 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 0.28 (9355 hom., cov: 33)
  • Exomes 𝑓: 0.15 (19214 hom.)
• Consequence: ZNF844 ENST00000441304.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 11 publications found

Genes affected

ZNF844 (HGNC:25932): (zinc finger protein 844) 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]

ENSG00000286098 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.9675097E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441304.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF844	NM_001136501.3	MANE Select	c.213T>C	p.Val71Val	synonymous	Exon 4 of 4	NP_001129973.1
	ZNF844	NR_134326.2		n.295T>C		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF844	ENST00000441304.2	TSL:1	c.152T>C	p.Leu51Ser	missense	Exon 3 of 3	ENSP00000402097.2
	ZNF844	ENST00000439326.8	TSL:1 MANE Select	c.213T>C	p.Val71Val	synonymous	Exon 4 of 4	ENSP00000392024.3
	ENSG00000286098	ENST00000652448.1		c.117T>C	p.Val39Val	synonymous	Exon 5 of 5	ENSP00000498410.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41823 AN: 152042 Hom.: 9313 Cov.: 33

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0764

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.249

GnomAD2 exomes AF: 0.166 AC: 18140 AN: 109232 AF XY: 0.158

Gnomad AFR exome AF: 0.629

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.0730

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.152 AC: 199041 AN: 1311306 Hom.: 19214 Cov.: 32 AF XY: 0.150 AC XY: 96365 AN XY: 640412

African (AFR) AF: 0.632 AC: 18004 AN: 28468

American (AMR) AF: 0.127 AC: 2532 AN: 19986

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 3654 AN: 20820

East Asian (EAS) AF: 0.0937 AC: 3215 AN: 34300

South Asian (SAS) AF: 0.148 AC: 9543 AN: 64338

European-Finnish (FIN) AF: 0.126 AC: 5869 AN: 46456

Middle Eastern (MID) AF: 0.226 AC: 1205 AN: 5324

European-Non Finnish (NFE) AF: 0.140 AC: 145577 AN: 1037658

Other (OTH) AF: 0.175 AC: 9442 AN: 53956

GnomAD4 genome AF: 0.275 AC: 41910 AN: 152160 Hom.: 9355 Cov.: 33 AF XY: 0.270 AC XY: 20116 AN XY: 74404

African (AFR) AF: 0.620 AC: 25754 AN: 41510

American (AMR) AF: 0.167 AC: 2547 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3470

East Asian (EAS) AF: 0.0764 AC: 396 AN: 5186

South Asian (SAS) AF: 0.148 AC: 713 AN: 4828

European-Finnish (FIN) AF: 0.129 AC: 1365 AN: 10572

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9643 AN: 68006

Other (OTH) AF: 0.250 AC: 527 AN: 2108

Alfa AF: 0.194 Hom.: 6822

Bravo AF: 0.292

TwinsUK AF: 0.146 AC: 542

ALSPAC AF: 0.157 AC: 604

ESP6500AA AF: 0.606 AC: 839

ESP6500EA AF: 0.131 AC: 416

ExAC AF: 0.126 AC: 13335

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.44
DANN	Benign	0.22
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.000010	N
LIST_S2	Benign	0.067	T
MetaRNN	Benign	0.000020	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.0
PROVEAN	Benign	3.0	N
REVEL	Benign	0.020
Sift	Benign	0.43	T
Sift4G	Benign	0.49	T
Vest4		0.013
ClinPred		0.00032	T
GERP RS		-0.94
Mutation Taster		=99/1	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: rs10424893; hg19: chr19-12186148; COSMIC: COSV71518160;