Variant X-46499920-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001190417.2(ZNF674):c.1654G>T(p.Asp552Tyr) variant causes a missense 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

ZNF674
NM_001190417.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.385

Variant links:

Genes affected

ZNF674 (HGNC:17625): (zinc finger protein 674) This gene encodes a zinc finger protein with an N-terminal Kruppel-associated box-containing (KRAB) domain and 11 Kruppel-type C2H2 zinc finger domains. Like other zinc finger proteins, this gene may function as a transcription factor. This gene resides on an area of chromosome X that has been implicated in nonsyndromic X-linked cognitive disabilities. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

ZNF674 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17248583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF674	NM_001190417.2 linkuse as main transcript	c.1654G>T	p.Asp552Tyr	missense_variant	6/6	ENST00000683375.1	NP_001177346.1
ZNF674	NM_001039891.3 linkuse as main transcript	c.1669G>T	p.Asp557Tyr	missense_variant	6/6		NP_001034980.1
ZNF674	NM_001146291.2 linkuse as main transcript	c.1651G>T	p.Asp551Tyr	missense_variant	6/6		NP_001139763.1
ZNF674	XM_011543943.4 linkuse as main transcript	c.1666G>T	p.Asp556Tyr	missense_variant	6/6		XP_011542245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF674	ENST00000683375.1 linkuse as main transcript	c.1654G>T	p.Asp552Tyr	missense_variant	6/6		NM_001190417.2	ENSP00000506769	A1
ZNF674	ENST00000523374.5 linkuse as main transcript	c.1669G>T	p.Asp557Tyr	missense_variant	6/6	1		ENSP00000429148	P4	Q2M3X9-1
ZNF674	ENST00000414387.6 linkuse as main transcript	c.1651G>T	p.Asp551Tyr	missense_variant	5/5	3		ENSP00000428248	A1	Q2M3X9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1066120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

342002

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.1669G>T (p.D557Y) alteration is located in exon 6 (coding exon 4) of the ZNF674 gene. This alteration results from a G to T substitution at nucleotide position 1669, causing the aspartic acid (D) at amino acid position 557 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.047

T;.

FATHMM_MKL

Benign

0.00025

LIST_S2

Benign

0.087

T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.35

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.047

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.98

D;.

Vest4

0.27

MutPred

0.51

Loss of disorder (P = 0.0255);.;

MVP

0.71

MPC

0.86

ClinPred

0.71

GERP RS

1.6

Varity_R

0.47

gMVP

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over