7-127374788-A-C

Position:

• chr7-127374788-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_176814.5(ZNF800):​c.548T>G​(p.Val183Gly) 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. 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)
• Consequence: ZNF800 NM_176814.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32

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 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=0.07126349).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF800	NM_176814.5	c.548T>G	p.Val183Gly	missense_variant	5/6	ENST00000265827.8	NP_789784.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF800	ENST00000265827.8	c.548T>G	p.Val183Gly	missense_variant	5/6	1	NM_176814.5	ENSP00000265827.3
ZNF800	ENST00000393312.5	c.548T>G	p.Val183Gly	missense_variant	5/6	5		ENSP00000376988.1
ZNF800	ENST00000393313.5	c.548T>G	p.Val183Gly	missense_variant	5/6	5		ENSP00000376989.1
ZNF800	ENST00000434602.5	c.548T>G	p.Val183Gly	missense_variant	5/5	5		ENSP00000403945.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Dec 07, 2024

The c.548T>G (p.V183G) alteration is located in exon 5 (coding exon 4) of the ZNF800 gene. This alteration results from a T to G substitution at nucleotide position 548, causing the valine (V) at amino acid position 183 to be replaced by a glycine (G). 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	0.087
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.78
DEOGEN2	Benign	0.0098	T;T;T;T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.57	.;.;T;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.071	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N;N;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.26	N;N;N;.;N
REVEL	Benign	0.022
Sift	Benign	0.30	T;T;T;.;D
Sift4G	Benign	0.40	T;T;T;T;T
Polyphen		0.0	B;B;B;.;.
Vest4		0.20
MutPred		0.26		Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);
MVP		0.043
MPC		0.31
ClinPred		0.085	T
GERP RS		2.0
Varity_R		0.051
gMVP		0.20

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.

Other links and lift over

hg19: chr7-127014842;