chr7-127374918-G-T

Position:

• chr7-127374918-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_176814.5(ZNF800):​c.418C>A​(p.Gln140Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ZNF800 NM_176814.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.50

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10413337).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF800	NM_176814.5	c.418C>A	p.Gln140Lys	missense_variant	5/6	ENST00000265827.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF800	ENST00000265827.8	c.418C>A	p.Gln140Lys	missense_variant	5/6	1	NM_176814.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461646 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727096

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

May 16, 2022

The c.418C>A (p.Q140K) alteration is located in exon 5 (coding exon 4) of the ZNF800 gene. This alteration results from a C to A substitution at nucleotide position 418, causing the glutamine (Q) at amino acid position 140 to be replaced by a lysine (K). 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	0.063
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.33
DEOGEN2	Benign	0.0070	T;T;T;T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.044
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;N;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.050	N;N;N;.;N
REVEL	Benign	0.098
Sift	Benign	0.99	T;T;T;.;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	B;B;B;.;.
Vest4		0.19
MutPred		0.51		Gain of ubiquitination at Q140 (P = 0.0075);Gain of ubiquitination at Q140 (P = 0.0075);Gain of ubiquitination at Q140 (P = 0.0075);Gain of ubiquitination at Q140 (P = 0.0075);Gain of ubiquitination at Q140 (P = 0.0075);
MVP		0.043
MPC		0.30
ClinPred		0.64	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.34

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: rs757790955; hg19: chr7-127014972;