10-75398970-G-T

Variant names:

• chr10-75398970-G-T
• rs1843741685
• NM_032772.6:c.1720C>A

Variant summary

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

The NM_032772.6(ZNF503):​c.1720C>A​(p.His574Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,706 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H574Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF503 NM_032772.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.61
• Publications: 0 publications found

Genes affected

ZNF503 (HGNC:23589): (zinc finger protein 503) Predicted to enable metal ion binding activity. Involved in G1 to G0 transition involved in cell differentiation; negative regulation of cell population proliferation; and negative regulation of gene expression. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000270087 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032772.6. 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
	ZNF503	NM_032772.6	MANE Select	c.1720C>A	p.His574Asn	missense	Exon 2 of 2	NP_116161.2
	ZNF503	NR_120651.2		n.812+2135C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF503	ENST00000372524.5	TSL:1 MANE Select	c.1720C>A	p.His574Asn	missense	Exon 2 of 2	ENSP00000361602.4	Q96F45-1
	ENSG00000270087	ENST00000418818.6	TSL:3	n.142+2135C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452706 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723040

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 86036

European-Finnish (FIN) AF: 0.0000217 AC: 1 AN: 46130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111016

Other (OTH) AF: 0.00 AC: 0 AN: 60178

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	0.0019	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.27
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.046	D
Polyphen		0.99	D
Vest4		0.68
MutPred		0.26		Loss of helix (P = 0.0558)
MVP		0.21
MPC		1.6
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.71
gMVP		0.73
Mutation Taster		=65/35	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: rs1843741685; hg19: chr10-77158728;