chrX-85255758-T-C

Variant names:

• chrX-85255758-T-C
• rs149845917
• NM_001330574.2:c.579T>C

Variant summary

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

The NM_001330574.2(ZNF711):​c.579T>C​(p.Asp193Asp) 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: 23)
• Consequence: ZNF711 NM_001330574.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.921
• Publications: 2 publications found

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]

ZNF711 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 97

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.58).
• BP7: Synonymous conserved (PhyloP=0.921 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330574.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF711	NM_001330574.2	MANE Select	c.579T>C	p.Asp193Asp	synonymous	Exon 5 of 11	NP_001317503.1
	ZNF711	NM_001375431.1		c.579T>C	p.Asp193Asp	synonymous	Exon 3 of 9	NP_001362360.1
	ZNF711	NM_001375432.1		c.579T>C	p.Asp193Asp	synonymous	Exon 5 of 11	NP_001362361.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF711	ENST00000674551.1	MANE Select	c.579T>C	p.Asp193Asp	synonymous	Exon 5 of 11	ENSP00000502839.1
	ZNF711	ENST00000360700.4	TSL:1	c.579T>C	p.Asp193Asp	synonymous	Exon 4 of 10	ENSP00000353922.4
	ZNF711	ENST00000276123.7	TSL:1	c.579T>C	p.Asp193Asp	synonymous	Exon 5 of 10	ENSP00000276123.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.5
DANN	Benign	0.50
PhyloP100		0.92

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: rs149845917; hg19: chrX-84510764; COSMIC: COSV99340797;