19-58246792-G-C

Variant names:

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

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>C​(p.Arg81Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 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: 0.0000021 (0 hom.)
• Consequence: ZNF544 NM_014480.4 missense, splice_region
• Scores: Splicing: ADA: 0.00006960
• 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=0.095930785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF544	NM_014480.4	c.242G>C	p.Arg81Pro	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>C	p.Arg81Pro	missense_variant, splice_region_variant	Exon 6 of 7		NM_014480.4	ENSP00000510489.1
ENSG00000283515	ENST00000637233.1	n.207G>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 6 of 12	5		ENSP00000490395.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 251092 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135690

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 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: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.039
DANN	Benign	0.95
DEOGEN2	Benign	0.0018	.;T;.;.;.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.18	T;.;T;T;T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.096	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L;.;.;.;L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.030	.;.;.;.;.;N
REVEL	Benign	0.028
Sift	Benign	0.078	.;.;.;.;.;T
Sift4G	Benign	0.14	T;D;T;T;T;D
Polyphen		0.71	.;P;.;.;.;P
Vest4		0.12, 0.16, 0.18, 0.16, 0.10
MutPred		0.39		Gain of glycosylation at R81 (P = 0.0112);Gain of glycosylation at R81 (P = 0.0112);Gain of glycosylation at R81 (P = 0.0112);Gain of glycosylation at R81 (P = 0.0112);Gain of glycosylation at R81 (P = 0.0112);Gain of glycosylation at R81 (P = 0.0112);
MVP		0.16
MPC		0.024
ClinPred		0.049	T
GERP RS		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.068
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000070
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.020		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;