rs139391034

Variant names:

• chr19-21182944-G-A
• rs139391034
• NM_133473.4:c.641G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-21182944-G-A
• chr19-21182944-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133473.4(ZNF431):​c.641G>A​(p.Cys214Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF431 NM_133473.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08927533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF431	NM_133473.4	c.641G>A	p.Cys214Tyr	missense_variant	Exon 5 of 5	ENST00000311048.11	NP_597730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF431	ENST00000311048.11	c.641G>A	p.Cys214Tyr	missense_variant	Exon 5 of 5	1	NM_133473.4	ENSP00000308578.6
ZNF431	ENST00000598331.1	c.761G>A	p.Cys254Tyr	missense_variant	Exon 6 of 6	5		ENSP00000471876.1
ZNF431	ENST00000600692.5	c.*228G>A		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000470668.1
ZNF431	ENST00000594425.5	c.97-6921G>A		intron_variant	Intron 2 of 2	2		ENSP00000469460.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461748 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.1
DANN	Benign	0.23
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.13	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.055	N;.
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-8.3	D;.
REVEL	Benign	0.052
Sift	Benign	0.38	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.058	B;.
Vest4		0.072
MutPred		0.25		Loss of disorder (P = 0.0613);.;
MVP		0.081
MPC		0.65
ClinPred		0.091	T
GERP RS		-1.6
Varity_R		0.18
gMVP		0.0099

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

Publications

LitVar

Other links and lift over

dbSNP: rs139391034; hg19: chr19-21365747;