chr19-12075333-T-C

Position:

• chr19-12075333-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000439326.8(ZNF844):​c.213T>C​(p.Val71=) variant causes a synonymous 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. 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 ENST00000439326.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.9675097E-5).
• BP7: Synonymous conserved (PhyloP=-1.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF844	NM_001136501.3	c.213T>C	p.Val71=	synonymous_variant	4/4	ENST00000439326.8	NP_001129973.1
ZNF844	NR_134326.2	n.295T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF844	ENST00000441304.2	c.152T>C	p.Leu51Ser	missense_variant	3/3	1		ENSP00000402097
ZNF844	ENST00000439326.8	c.213T>C	p.Val71=	synonymous_variant	4/4	1	NM_001136501.3	ENSP00000392024	P1
ZNF844	ENST00000550826.1	c.-259T>C		5_prime_UTR_variant	2/2	3		ENSP00000448588

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

GnomAD3 exomes AF: 0.166 AC: 18140 AN: 109232 Hom.: 2494 AF XY: 0.158 AC XY: 9169 AN XY: 57874

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 SAS exome AF: 0.148

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

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.0937

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.175

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

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0764

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.250

Alfa AF: 0.195 Hom.: 1464

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 v4.3

Name	Calibrated prediction	Score	Prediction
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
MutationTaster	Benign	1.0	P;P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10424893; hg19: chr19-12186148; COSMIC: COSV71518160;