19-9161293-C-G

Variant names:

• chr19-9161293-C-G
• rs9305035
• NM_020933.5:c.1648C>G

Variant summary

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

The NM_020933.5(ZNF317):​c.1648C>G​(p.Arg550Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,452,170 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ZNF317 NM_020933.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 7 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF317	NM_020933.5	c.1648C>G	p.Arg550Gly	missense_variant	Exon 7 of 7	ENST00000247956.11	NP_065984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF317	ENST00000247956.11	c.1648C>G	p.Arg550Gly	missense_variant	Exon 7 of 7	1	NM_020933.5	ENSP00000247956.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1452170 Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2 AN XY: 722044

African (AFR) AF: 0.00 AC: 0 AN: 33328

American (AMR) AF: 0.00 AC: 0 AN: 42556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39246

South Asian (SAS) AF: 0.00 AC: 0 AN: 84174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1107696

Other (OTH) AF: 0.00 AC: 0 AN: 60084

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0065	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.4	M;.
PhyloP100		-1.3
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.2	D;D
REVEL	Benign	0.12
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;D
Vest4		0.57
MutPred		0.64		Loss of catalytic residue at R550 (P = 0.0107);.;
MVP		0.27
MPC		1.5
ClinPred		0.97	D
GERP RS		1.7
Varity_R		0.47
gMVP		0.38
Mutation Taster		=86/14	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

dbSNP: rs9305035; hg19: chr19-9271969;