Variant 7-127374170-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_176814.5(ZNF800):c.1166C>G(p.Thr389Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,486 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ZNF800
NM_176814.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

ZNF800 (HGNC:27267): (zinc finger protein 800) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF800 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049069196).

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF800	NM_176814.5 linkuse as main transcript	c.1166C>G	p.Thr389Arg	missense_variant	5/6	ENST00000265827.8	NP_789784.2	Q2TB10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF800	ENST00000265827.8 linkuse as main transcript	c.1166C>G	p.Thr389Arg	missense_variant	5/6	1	NM_176814.5	ENSP00000265827.3	Q2TB10
ZNF800	ENST00000393312.5 linkuse as main transcript	c.1166C>G	p.Thr389Arg	missense_variant	5/6	5		ENSP00000376988.1	Q2TB10
ZNF800	ENST00000393313.5 linkuse as main transcript	c.1166C>G	p.Thr389Arg	missense_variant	5/6	5		ENSP00000376989.1	Q2TB10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000520

AC:

AN:

250070

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000378

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:

0.00000958

AC:

AN:

1461486

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000314

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.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000577

AC:

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

Jul 31, 2024

The c.1166C>G (p.T389R) alteration is located in exon 5 (coding exon 4) of the ZNF800 gene. This alteration results from a C to G substitution at nucleotide position 1166, causing the threonine (T) at amino acid position 389 to be replaced by an arginine (R). 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

0.079

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0044

T;T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.048

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.84

.;.;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.34

N;N;N

REVEL

Benign

0.062

Sift

Benign

0.39

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.016

B;B;B

Vest4

0.28

MutPred

0.41

Gain of MoRF binding (P = 0.0105);Gain of MoRF binding (P = 0.0105);Gain of MoRF binding (P = 0.0105);

MVP

0.043

MPC

0.27

ClinPred

0.039

GERP RS

3.9

Varity_R

0.044

gMVP

0.27

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over