rs571507375

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-58244034-G-A
• chr19-58244034-G-C
• chr19-58244034-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014480.4(ZNF544):​c.11G>A​(p.Arg4His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000553 in 1,608,342 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: ZNF544 NM_014480.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08116642).

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>A	p.Arg4His	missense	Exon 4 of 7	NP_055295.2	Q6NX49
	ZNF544	NM_001387410.1		c.173G>A	p.Arg58His	missense	Exon 5 of 8	NP_001374339.1
	ZNF544	NM_001387413.1		c.173G>A	p.Arg58His	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>A	p.Arg4His	missense	Exon 4 of 7	ENSP00000510489.1	Q6NX49
	ZNF544	ENST00000269829.5	TSL:1	c.11G>A	p.Arg4His	missense	Exon 1 of 4	ENSP00000269829.4	Q6NX49
	ZNF544	ENST00000596652.5	TSL:1	c.11G>A	p.Arg4His	missense	Exon 3 of 6	ENSP00000469635.1	Q6NX49

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152100 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000284 AC: 7 AN: 246494 AF XY: 0.0000300

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000307

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000577 AC: 84 AN: 1456242 Hom.: 0 Cov.: 30 AF XY: 0.0000511 AC XY: 37 AN XY: 724218

African (AFR) AF: 0.00 AC: 0 AN: 33378

American (AMR) AF: 0.0000228 AC: 1 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: 0.0000589 AC: 5 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: 0.0000649 AC: 72 AN: 1109240

Other (OTH) AF: 0.0000997 AC: 6 AN: 60204

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152100 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74282

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000494 Hom.: 0

Bravo AF: 0.0000264

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.033
DANN	Benign	0.83
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.00067	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.86	L
PhyloP100		-1.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.0090
Sift	Benign	0.047	D
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.073
MVP		0.14
MPC		0.022
ClinPred		0.016	T
GERP RS		-1.5
PromoterAI		0.00010	Neutral
Varity_R		0.024
gMVP		0.10
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;