8-37697778-G-C

Position:

• chr8-37697778-G-C

Variant summary

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

The NM_025069.3(ZNF703):​c.877G>C​(p.Val293Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF703 NM_025069.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.77

Genes affected

ZNF703 (HGNC:25883): (zinc finger protein 703) Predicted to enable DNA-binding transcription factor binding activity. Involved in several processes, including cellular response to estradiol stimulus; mammary gland epithelial cell differentiation; and positive regulation of mammary gland epithelial cell proliferation. Located in cytoplasm and nuclear matrix. Part of protein-containing complex. [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=0.25195524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF703	NM_025069.3	c.877G>C	p.Val293Leu	missense_variant	2/2	ENST00000331569.6	NP_079345.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF703	ENST00000331569.6	c.877G>C	p.Val293Leu	missense_variant	2/2	1	NM_025069.3	ENSP00000332325	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Jan 19, 2022

The c.877G>C (p.V293L) alteration is located in exon 2 (coding exon 2) of the ZNF703 gene. This alteration results from a G to C substitution at nucleotide position 877, causing the valine (V) at amino acid position 293 to be replaced by a leucine (L). 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.99	D
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Uncertain	0.029	D
Sift4G	Benign	0.33	T
Polyphen		0.89	P
Vest4		0.17
MutPred		0.15		Loss of glycosylation at S297 (P = 0.2445);
MVP		0.42
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.35
gMVP		0.48

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: rs1802097071; hg19: chr8-37555296;