rs199422240

Variant names:

• chrX-85271115-A-G
• rs199422240
• NM_001330574.2:c.1711A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-85271115-A-G
• chrX-85271115-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001330574.2(ZNF711):​c.1711A>G​(p.Arg571Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,434 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ZNF711 NM_001330574.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

Genes affected

ZNF711 (HGNC:13128): (zinc finger protein 711) This gene encodes a zinc finger protein of unknown function. It bears similarity to a zinc finger protein which acts as a transcriptional activator. This gene lies in a region of the X chromosome which has been associated with cognitive disability. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF711	NM_001330574.2	c.1711A>G	p.Arg571Gly	missense_variant	Exon 11 of 11	ENST00000674551.1	NP_001317503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF711	ENST00000674551.1	c.1711A>G	p.Arg571Gly	missense_variant	Exon 11 of 11		NM_001330574.2	ENSP00000502839.1
ZNF711	ENST00000360700.4	c.1711A>G	p.Arg571Gly	missense_variant	Exon 10 of 10	1		ENSP00000353922.4
ZNF711	ENST00000276123.7	c.1573A>G	p.Arg525Gly	missense_variant	Exon 10 of 10	1		ENSP00000276123.3
ZNF711	ENST00000373165.7	c.1573A>G	p.Arg525Gly	missense_variant	Exon 9 of 9	1		ENSP00000362260.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097434 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363130

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: 0.00

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;T;.
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.1	M;M;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.9	D;D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.79
MutPred		0.79		Loss of methylation at K522 (P = 0.0559);Loss of methylation at K522 (P = 0.0559);.;
MVP		0.94
MPC		1.6
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.85
gMVP		0.85

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: rs199422240; hg19: chrX-84526121;