19-9160793-A-G

Variant summary

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

The NM_020933.5(ZNF317):c.1148A>G(p.Asn383Ser) 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. 13/21 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: ZNF317 NM_020933.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.143

Genes affected

ZNF317 (HGNC:13507): (zinc finger protein 317) 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. 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=0.14555341).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF317	NM_020933.5	c.1148A>G	p.Asn383Ser	missense_variant	7/7	ENST00000247956.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF317	ENST00000247956.11	c.1148A>G	p.Asn383Ser	missense_variant	7/7	1	NM_020933.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Aug 14, 2023

The c.1148A>G (p.N383S) alteration is located in exon 7 (coding exon 6) of the ZNF317 gene. This alteration results from a A to G substitution at nucleotide position 1148, causing the asparagine (N) at amino acid position 383 to be replaced by a serine (S). 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	0.26
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	19
Dann	Uncertain	1.0
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.93	N;.
MutationTaster	Benign	0.88	N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.010	N;N
REVEL	Benign	0.099
Sift	Benign	0.38	T;D
Sift4G	Uncertain	0.029	D;D
Polyphen		1.0	D;P
Vest4		0.21
MutPred		0.43		Gain of disorder (P = 0.0866);.;
MVP		0.23
MPC		1.2
ClinPred		0.74	D
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.045

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: chr19-9271469;