10-75401327-G-C

Variant names:

• chr10-75401327-G-C
• NM_032772.6:c.93C>G
• ZNF503 p.Ala31Ala

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The NM_032772.6(ZNF503):​c.93C>G​(p.Ala31Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A31A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF503 NM_032772.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16
• 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]

ZNF503-AS2 (HGNC:23525): (ZNF503 antisense RNA 2)

ENSG00000270087 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP7: Synonymous conserved (PhyloP=2.16 with no splicing effect.

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.93C>G	p.Ala31Ala	synonymous	Exon 1 of 2	NP_116161.2
	ZNF503	NR_120651.2		n.590C>G		non_coding_transcript_exon	Exon 1 of 4
	ZNF503-AS2	NR_024421.1		n.-201G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF503	ENST00000372524.5	TSL:1 MANE Select	c.93C>G	p.Ala31Ala	synonymous	Exon 1 of 2	ENSP00000361602.4	Q96F45-1
	ZNF503-AS2	ENST00000725121.1		n.182+184G>C		intron	N/A
	ZNF503-AS2	ENST00000725138.1		n.106+184G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		2.2
PromoterAI		-0.038	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-77161085;