Genetic Variant NM_001190417.2:c.1606A>G (chrX-46499968-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001190417.2(ZNF674):c.1606A>G(p.Ile536Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,199,183 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

ZNF674
NM_001190417.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.233

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=0.09295991).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF674	NM_001190417.2 link	c.1606A>G	p.Ile536Val	missense_variant	Exon 6 of 6	ENST00000683375.1	NP_001177346.1	Q2M3X9A0A804HHU7
ZNF674	NM_001039891.3 link	c.1621A>G	p.Ile541Val	missense_variant	Exon 6 of 6		NP_001034980.1	Q2M3X9-1
ZNF674	NM_001146291.2 link	c.1603A>G	p.Ile535Val	missense_variant	Exon 6 of 6		NP_001139763.1	Q2M3X9-2
ZNF674	XM_011543943.4 link	c.1618A>G	p.Ile540Val	missense_variant	Exon 6 of 6		XP_011542245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF674	ENST00000683375.1 link	c.1606A>G	p.Ile536Val	missense_variant	Exon 6 of 6		NM_001190417.2	ENSP00000506769.1	A0A804HHU7
ZNF674	ENST00000523374.5 link	c.1621A>G	p.Ile541Val	missense_variant	Exon 6 of 6	1		ENSP00000429148.1	Q2M3X9-1
ZNF674	ENST00000414387.6 link	c.1603A>G	p.Ile535Val	missense_variant	Exon 5 of 5	3		ENSP00000428248.1	Q2M3X9-2

Frequencies

GnomAD3 genomes

AF:

0.0000184

AC:

AN:

108489

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31861

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000195

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000576

AC:

AN:

173607

Hom.:

AF XY:

0.00

AC XY:

AN XY:

59651

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000375

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.17e-7

AC:

AN:

1090694

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

357206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000288

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

AF:

0.0000184

AC:

AN:

108489

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31861

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000195

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.96

CADD

Benign

8.9

DANN

Benign

0.67

DEOGEN2

Benign

0.0050

T;.

FATHMM_MKL

Benign

0.000050

LIST_S2

Benign

0.26

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.33

N;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.014

Sift

Benign

0.21

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.24

B;.

Vest4

0.024

MutPred

0.34

Gain of disorder (P = 0.0991);.;

MVP

0.54

MPC

0.29

ClinPred

0.028

GERP RS

1.2

Varity_R

0.082

gMVP

0.017

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over