19-58244034-G-T

Variant names:

• chr19-58244034-G-T
• rs571507375
• NM_014480.4:c.11G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014480.4(ZNF544):​c.11G>T​(p.Arg4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,608,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF544 NM_014480.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04983601).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014480.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF544	NM_014480.4	MANE Select	c.11G>T	p.Arg4Leu	missense	Exon 4 of 7	NP_055295.2	Q6NX49
	ZNF544	NM_001387410.1		c.173G>T	p.Arg58Leu	missense	Exon 5 of 8	NP_001374339.1
	ZNF544	NM_001387413.1		c.173G>T	p.Arg58Leu	missense	Exon 5 of 8	NP_001374342.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF544	ENST00000687789.1	MANE Select	c.11G>T	p.Arg4Leu	missense	Exon 4 of 7	ENSP00000510489.1	Q6NX49
	ZNF544	ENST00000269829.5	TSL:1	c.11G>T	p.Arg4Leu	missense	Exon 1 of 4	ENSP00000269829.4	Q6NX49
	ZNF544	ENST00000596652.5	TSL:1	c.11G>T	p.Arg4Leu	missense	Exon 3 of 6	ENSP00000469635.1	Q6NX49

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152100 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000122 AC: 3 AN: 246494 AF XY: 0.00000751

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000275 AC: 4 AN: 1456242 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724218

African (AFR) AF: 0.000120 AC: 4 AN: 33378

American (AMR) AF: 0.00 AC: 0 AN: 43816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39416

South Asian (SAS) AF: 0.00 AC: 0 AN: 84956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109240

Other (OTH) AF: 0.00 AC: 0 AN: 60204

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152216 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74410

African (AFR) AF: 0.000168 AC: 7 AN: 41548

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0070
DANN	Benign	0.76
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.00094	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.22	N
PhyloP100		-1.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.0010
Sift	Benign	0.055	T
Sift4G	Benign	0.26	T
Polyphen		0.078	B
Vest4		0.17
MutPred		0.36		Loss of methylation at R4 (P = 0.0306)
MVP		0.099
MPC		0.022
ClinPred		0.015	T
GERP RS		-1.5
PromoterAI		-0.012	Neutral
Varity_R		0.048
gMVP		0.17
Mutation Taster		=99/1	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: rs571507375; hg19: chr19-58755400;