X-47976226-C-T

Variant names:

• chrX-47976226-C-T
• NM_001007088.2:c.1804G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001007088.2(ZNF182):​c.1804G>A​(p.Ala602Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000935 in 1,069,350 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 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. A602S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: ZNF182 NM_001007088.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

Genes affected

ZNF182 (HGNC:13001): (zinc finger protein 182) Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This gene encodes a zinc finger protein, and belongs to the krueppel C2H2-type zinc-finger protein family. It may be involved in transcriptional regulation. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, May 2010]

ZNF81 (HGNC:13156): (zinc finger protein 81) This gene encodes a protein that likely functions as a transcription factor. The protein contains an N-terminal KRAB domain and several C2H2-type zinc finger motifs. Mutations in this gene cause an X-linked form of intellectual disability (MRX45). Microduplication of a region of chromosome X including this gene has also been associated with other forms of intellectual disability. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059295803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF182	NM_001007088.2	c.1804G>A	p.Ala602Thr	missense_variant	Exon 6 of 6	ENST00000376943.8	NP_001007089.1
ZNF182	NM_001178099.2	c.1861G>A	p.Ala621Thr	missense_variant	Exon 7 of 7		NP_001171570.1
ZNF182	NM_006962.2	c.1861G>A	p.Ala621Thr	missense_variant	Exon 7 of 7		NP_008893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF182	ENST00000376943.8	c.1804G>A	p.Ala602Thr	missense_variant	Exon 6 of 6	1	NM_001007088.2	ENSP00000366142.4
ZNF182	ENST00000396965.5	c.1861G>A	p.Ala621Thr	missense_variant	Exon 7 of 7	2		ENSP00000380165.1
ZNF81	ENST00000376950.4	c.278-26302C>T		intron_variant	Intron 4 of 4	5		ENSP00000366149.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.35e-7 AC: 1 AN: 1069350 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 347220

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: 0.00000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.3
DANN	Benign	0.86
DEOGEN2	Benign	0.0033	.;T
FATHMM_MKL	Benign	0.00030	N
LIST_S2	Benign	0.040	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.72	.;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	2.9	N;N
REVEL	Benign	0.045
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	.;B
Vest4		0.14
MutPred		0.46		.;Gain of phosphorylation at A621 (P = 0.0472);
MVP		0.15
MPC		0.40
ClinPred		0.046	T
GERP RS		1.1
Varity_R		0.039
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-47835625;