chr7-127373387-C-T

Position:

• chr7-127373387-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_176814.5(ZNF800):​c.1949G>A​(p.Gly650Glu) 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: 32)
• Consequence: ZNF800 NM_176814.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062965006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF800	NM_176814.5	c.1949G>A	p.Gly650Glu	missense_variant	5/6	ENST00000265827.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF800	ENST00000265827.8	c.1949G>A	p.Gly650Glu	missense_variant	5/6	1	NM_176814.5	P1
ZNF800	ENST00000393312.5	c.1949G>A	p.Gly650Glu	missense_variant	5/6	5		P1
ZNF800	ENST00000393313.5	c.1949G>A	p.Gly650Glu	missense_variant	5/6	5		P1
ZNF800	ENST00000485577.1	n.179G>A		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.1949G>A (p.G650E) alteration is located in exon 5 (coding exon 4) of the ZNF800 gene. This alteration results from a G to A substitution at nucleotide position 1949, causing the glycine (G) at amino acid position 650 to be replaced by a glutamic acid (E). 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	0.078
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.0045	T;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	0.011
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.063	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N;N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.35	N;N;N
REVEL	Benign	0.068
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.83	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.097
MutPred		0.21		Loss of MoRF binding (P = 0.0432);Loss of MoRF binding (P = 0.0432);Loss of MoRF binding (P = 0.0432);
MVP		0.043
MPC		0.31
ClinPred		0.46	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.056
gMVP		0.29

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

Other links and lift over

dbSNP: rs1432058861; hg19: chr7-127013441;