Genetic Variant NM_001330574.2:c.1630G>C (chrX-85271034-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001330574.2(ZNF711):c.1630G>C(p.Val544Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,745 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. V544A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

ZNF711
NM_001330574.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.03

Publications

0 publications found

Variant links:

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

ZNF711 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF711	NM_001330574.2 link	c.1630G>C	p.Val544Leu	missense_variant	Exon 11 of 11	ENST00000674551.1	NP_001317503.1	Q9Y462-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF711	ENST00000674551.1 link	c.1630G>C	p.Val544Leu	missense_variant	Exon 11 of 11		NM_001330574.2	ENSP00000502839.1	Q9Y462-3
ZNF711	ENST00000360700.4 link	c.1630G>C	p.Val544Leu	missense_variant	Exon 10 of 10	1		ENSP00000353922.4	Q9Y462-3
ZNF711	ENST00000276123.7 link	c.1492G>C	p.Val498Leu	missense_variant	Exon 10 of 10	1		ENSP00000276123.3	Q9Y462-1
ZNF711	ENST00000373165.7 link	c.1492G>C	p.Val498Leu	missense_variant	Exon 9 of 9	1		ENSP00000362260.3	Q9Y462-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1097745

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363359

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26364

American (AMR)

AF:

0.00

AC:

AN:

35119

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19374

East Asian (EAS)

AF:

0.00

AC:

AN:

30183

South Asian (SAS)

AF:

0.00

AC:

AN:

54132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000356

AC:

AN:

841883

Other (OTH)

AF:

0.00

AC:

AN:

46060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

T;T;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

.;D;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.11

N;N;.

PhyloP100

8.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.26

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.95

P;P;D

Vest4

0.62

MutPred

0.58

Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);.;

MVP

0.55

MPC

1.4

ClinPred

0.96

GERP RS

5.2

Varity_R

0.52

gMVP

0.75

Mutation Taster

=69/31

polymorphism

(source)

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

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NM_001330574.2:c.1630G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over