rs371902876

Variant names:

• chrX-47976318-C-A
• rs371902876
• NM_001007088.2:c.1712G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-47976318-C-A
• chrX-47976318-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001007088.2(ZNF182):​c.1712G>T​(p.Arg571Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,204,787 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts 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. R571K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000011 (0 hom. 3 hem.)
• Consequence: ZNF182 NM_001007088.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 5 publications found

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]

ZNF81 Gene-Disease associations (from GenCC):

• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, X-linked 45

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• X-linked intellectual disability

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30931157).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007088.2. 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
	ZNF182	NM_001007088.2	MANE Select	c.1712G>T	p.Arg571Ile	missense	Exon 6 of 6	NP_001007089.1	P17025-2
	ZNF182	NM_001178099.2		c.1769G>T	p.Arg590Ile	missense	Exon 7 of 7	NP_001171570.1	P17025-1
	ZNF182	NM_006962.2		c.1769G>T	p.Arg590Ile	missense	Exon 7 of 7	NP_008893.1	P17025-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF182	ENST00000376943.8	TSL:1 MANE Select	c.1712G>T	p.Arg571Ile	missense	Exon 6 of 6	ENSP00000366142.4	P17025-2
	ZNF182	ENST00000396965.5	TSL:2	c.1769G>T	p.Arg590Ile	missense	Exon 7 of 7	ENSP00000380165.1	P17025-1
	ZNF182	ENST00000897864.1		c.1712G>T	p.Arg571Ile	missense	Exon 5 of 5	ENSP00000567923.1

Frequencies

GnomAD3 genomes AF: 0.00000896 AC: 1 AN: 111606 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000115 AC: 2 AN: 174559 AF XY: 0.0000167

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000254

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 12 AN: 1093181 Hom.: 0 Cov.: 31 AF XY: 0.00000835 AC XY: 3 AN XY: 359131

African (AFR) AF: 0.00 AC: 0 AN: 26216

American (AMR) AF: 0.00 AC: 0 AN: 34296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19047

East Asian (EAS) AF: 0.00 AC: 0 AN: 30164

South Asian (SAS) AF: 0.00 AC: 0 AN: 52793

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40407

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4098

European-Non Finnish (NFE) AF: 0.0000143 AC: 12 AN: 840243

Other (OTH) AF: 0.00 AC: 0 AN: 45917

GnomAD4 genome AF: 0.00000896 AC: 1 AN: 111606 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33778

African (AFR) AF: 0.00 AC: 0 AN: 30678

American (AMR) AF: 0.00 AC: 0 AN: 10542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3552

South Asian (SAS) AF: 0.00 AC: 0 AN: 2634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6003

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53124

Other (OTH) AF: 0.00 AC: 0 AN: 1503

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.080
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.36
MVP		0.37
MPC		1.7
ClinPred		0.91	D
GERP RS		4.9
Varity_R		0.68
gMVP		0.35
Mutation Taster		=94/6	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: rs371902876; hg19: chrX-47835717; COSMIC: COSV59355832;