19-58246792-G-T

Variant names:

• chr19-58246792-G-T
• rs576820348
• NM_014480.4:c.242G>T

Variant summary

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

The NM_014480.4(ZNF544):​c.242G>T​(p.Arg81Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF544 NM_014480.4 missense, splice_region
• Scores: Splicing: ADA: 0.0007821
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

Genes affected

ZNF544 (HGNC:16759): (zinc finger protein 544) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-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]

ENSG00000283515 (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=0.07224816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF544	NM_014480.4	c.242G>T	p.Arg81Leu	missense_variant, splice_region_variant	Exon 6 of 7	ENST00000687789.1	NP_055295.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF544	ENST00000687789.1	c.242G>T	p.Arg81Leu	missense_variant, splice_region_variant	Exon 6 of 7		NM_014480.4	ENSP00000510489.1
ENSG00000283515	ENST00000637233.1	n.207G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 6 of 12	5		ENSP00000490395.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251092 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135690

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461570 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.10
DANN	Benign	0.97
DEOGEN2	Benign	0.0057	.;T;.;.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.22	T;.;T;T;T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.072	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	.;L;.;.;.;L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.4	.;.;.;.;.;N
REVEL	Benign	0.021
Sift	Benign	0.14	.;.;.;.;.;T
Sift4G	Benign	0.26	T;T;T;T;T;T
Polyphen		0.26	.;B;.;.;.;B
Vest4		0.22, 0.20, 0.20, 0.20, 0.19
MutPred		0.42		Gain of catalytic residue at R81 (P = 0.0012);Gain of catalytic residue at R81 (P = 0.0012);Gain of catalytic residue at R81 (P = 0.0012);Gain of catalytic residue at R81 (P = 0.0012);Gain of catalytic residue at R81 (P = 0.0012);Gain of catalytic residue at R81 (P = 0.0012);
MVP		0.11
MPC		0.022
ClinPred		0.048	T
GERP RS		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.036
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00078
dbscSNV1_RF	Benign	0.042
SpliceAI score (max)		0.14		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: rs576820348; hg19: chr19-58758158;