rs10424893

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-12075333-T-A
• chr19-12075333-T-C

Variant summary

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

The ENST00000441304.2(ZNF844):​c.152T>A​(p.Leu51*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,312,012 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ZNF844 ENST00000441304.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF844	NM_001136501.3	c.213T>A	p.Val71Val	synonymous_variant	Exon 4 of 4	ENST00000439326.8	NP_001129973.1
ZNF844	NR_134326.2	n.295T>A		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF844	ENST00000439326.8	c.213T>A	p.Val71Val	synonymous_variant	Exon 4 of 4	1	NM_001136501.3	ENSP00000392024.3
ENSG00000286098	ENST00000652448.1	c.117T>A	p.Val39Val	synonymous_variant	Exon 5 of 5			ENSP00000498410.1
ENSG00000286132	ENST00000651606.1	n.6T>A		non_coding_transcript_exon_variant	Exon 1 of 5			ENSP00000498244.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1312012 Hom.: 0 Cov.: 32 AF XY: 0.00000312 AC XY: 2 AN XY: 640764

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28502

American (AMR) AF: 0.00 AC: 0 AN: 19996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20838

East Asian (EAS) AF: 0.00 AC: 0 AN: 34306

South Asian (SAS) AF: 0.0000311 AC: 2 AN: 64406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5330

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1038148

Other (OTH) AF: 0.00 AC: 0 AN: 53988

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.40
DANN	Benign	0.88
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.000070	N
PhyloP100		-1.0
Vest4		0.024
GERP RS		-0.94
Mutation Taster		=188/12	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: rs10424893; hg19: chr19-12186148;