8-144841650-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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: 33)
• Consequence: ZNF7 NM_003416.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.592

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

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=0.07012224).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF7	NM_003416.4	c.543T>G	p.Cys181Trp	missense_variant	Exon 5 of 5	ENST00000532777.6	NP_003407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF7	ENST00000532777.6	c.543T>G	p.Cys181Trp	missense_variant	Exon 5 of 5	1	NM_003416.4	ENSP00000432641.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.543T>G (p.C181W) alteration is located in exon 5 (coding exon 4) of the ZNF7 gene. This alteration results from a T to G substitution at nucleotide position 543, causing the cysteine (C) at amino acid position 181 to be replaced by a tryptophan (W). 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	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.033	T;.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.64	T;T;T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.070	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	.;.;.;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.0020	.;.;.;B
Vest4		0.31, 0.32, 0.32
MutPred		0.17		Loss of helix (P = 0.1299);.;.;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

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: chr8-146067035;