19-12075352-A-T

Variant names:

• chr19-12075352-A-T
• rs765905542
• NM_001136501.3:c.232A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136501.3(ZNF844):​c.232A>T​(p.Asn78Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,358,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ZNF844 NM_001136501.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00800

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08627951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF844	NM_001136501.3	c.232A>T	p.Asn78Tyr	missense_variant	Exon 4 of 4	ENST00000439326.8	NP_001129973.1
ZNF844	NR_134326.2	n.314A>T		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.232A>T	p.Asn78Tyr	missense_variant	Exon 4 of 4	1	NM_001136501.3	ENSP00000392024.3
ENSG00000286098	ENST00000652448.1	c.136A>T	p.Asn46Tyr	missense_variant	Exon 5 of 5			ENSP00000498410.1
ENSG00000286132	ENST00000651606.1	n.25A>T		non_coding_transcript_exon_variant	Exon 1 of 5			ENSP00000498244.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000708 AC: 1 AN: 141314 Hom.: 0 AF XY: 0.0000131 AC XY: 1 AN XY: 76268

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000158

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1358602 Hom.: 0 Cov.: 32 AF XY: 0.00000299 AC XY: 2 AN XY: 668952

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000352 Hom.: 0

ExAC AF: 0.00000858 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.232A>T (p.N78Y) alteration is located in exon 4 (coding exon 4) of the ZNF844 gene. This alteration results from a A to T substitution at nucleotide position 232, causing the asparagine (N) at amino acid position 78 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.94
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00015	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.00076	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.99	T
PROVEAN	Benign	0.69	N
REVEL	Benign	0.021
Sift	Benign	0.13	T
Sift4G	Benign	0.27	T
Vest4		0.14
MutPred		0.47		Loss of methylation at K57 (P = 0.003);
MVP		0.014
ClinPred		0.034	T
GERP RS		-0.91

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: rs765905542; hg19: chr19-12186167;