rs553260809

Variant names:

• chr19-21183116-G-A
• rs553260809
• NM_133473.4:c.813G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-21183116-G-A
• chr19-21183116-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_133473.4(ZNF431):​c.813G>A​(p.Gln271Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF431 NM_133473.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.76
• Publications: 0 publications found

Genes affected

ZNF431 (HGNC:20809): (zinc finger protein 431) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein may negatively regulate transcription of target genes, including the hedgehog signaling pathway receptor patched 1, by interacting with histone deacetylases. Mutations in this gene may be associated with non-syndromic facial clefting in human patients. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-3.76 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133473.4. 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
	ZNF431	NM_133473.4	MANE Select	c.813G>A	p.Gln271Gln	synonymous	Exon 5 of 5	NP_597730.2	Q8TF32
	ZNF431	NM_001319124.2		c.816G>A	p.Gln272Gln	synonymous	Exon 5 of 5	NP_001306053.1
	ZNF431	NM_001319126.2		c.540G>A	p.Gln180Gln	synonymous	Exon 6 of 6	NP_001306055.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF431	ENST00000311048.11	TSL:1 MANE Select	c.813G>A	p.Gln271Gln	synonymous	Exon 5 of 5	ENSP00000308578.6	Q8TF32
	ZNF431	ENST00000949855.1		c.936G>A	p.Gln312Gln	synonymous	Exon 6 of 6	ENSP00000619914.1
	ZNF431	ENST00000949854.1		c.864G>A	p.Gln288Gln	synonymous	Exon 6 of 6	ENSP00000619913.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.34
PhyloP100		-3.8

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: rs553260809; hg19: chr19-21365919;