NM_003416.4:c.543T>G

Variant names:

• chr8-144841650-T-G
• NM_003416.4:c.543T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003416.4(ZNF7):​c.543T>G​(p.Cys181Trp) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF7 NM_003416.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.592
• Publications: 0 publications found

Genes affected

ZNF7 (HGNC:13139): (zinc finger protein 7) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

COMMD5 (HGNC:17902): (COMM domain containing 5) Predicted to be involved in proximal tubule morphogenesis. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07012224).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003416.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF7	NM_003416.4	MANE Select	c.543T>G	p.Cys181Trp	missense	Exon 5 of 5	NP_003407.1	P17097-1
	ZNF7	NM_001349809.2		c.606T>G	p.Cys202Trp	missense	Exon 4 of 4	NP_001336738.1
	ZNF7	NM_001349806.2		c.594T>G	p.Cys198Trp	missense	Exon 5 of 5	NP_001336735.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF7	ENST00000532777.6	TSL:1 MANE Select	c.543T>G	p.Cys181Trp	missense	Exon 5 of 5	ENSP00000432641.2	P17097-1
	ZNF7	ENST00000446747.7	TSL:1	c.576T>G	p.Cys192Trp	missense	Exon 5 of 5	ENSP00000393260.2	P17097-2
	ZNF7	ENST00000528372.5	TSL:1	c.543T>G	p.Cys181Trp	missense	Exon 5 of 5	ENSP00000432724.1	P17097-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.59
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.15
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		0.0020	B
Vest4		0.31
MutPred		0.17		Loss of helix (P = 0.1299)
MVP		0.13
MPC		0.16
ClinPred		0.036	T
GERP RS		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.082
gMVP		0.11
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chr8-146067035;