19-9160161-C-G

Variant names:

• chr19-9160161-C-G
• rs761951507
• NM_020933.5:c.516C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020933.5(ZNF317):​c.516C>G​(p.Phe172Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF317 NM_020933.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.664
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05314058).
• BP6: Variant 19-9160161-C-G is Benign according to our data. Variant chr19-9160161-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3335436.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020933.5. 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
	ZNF317	NM_020933.5	MANE Select	c.516C>G	p.Phe172Leu	missense	Exon 7 of 7	NP_065984.3
	ZNF317	NM_001190791.2		c.420C>G	p.Phe140Leu	missense	Exon 6 of 6	NP_001177720.1	Q96PQ6-2
	ZNF317	NR_102435.2		n.950C>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF317	ENST00000247956.11	TSL:1 MANE Select	c.516C>G	p.Phe172Leu	missense	Exon 7 of 7	ENSP00000247956.5	Q96PQ6-1
	ZNF317	ENST00000360385.7	TSL:1	c.420C>G	p.Phe140Leu	missense	Exon 6 of 6	ENSP00000353554.2	Q96PQ6-2
	ZNF317	ENST00000591278.5	TSL:1	n.*341C>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000465780.1	K7EKT9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251390 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	Pathogenic	0.62
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.53
DANN	Benign	0.43
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.00085	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.99	L
PhyloP100		-0.66
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.036
Sift	Benign	0.66	T
Sift4G	Benign	0.46	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.55		Gain of disorder (P = 0.1465)
MVP		0.088
MPC		0.53
ClinPred		0.0077	T
GERP RS		-1.9
Varity_R		0.026
gMVP		0.25
Mutation Taster		=91/9	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: rs761951507; hg19: chr19-9270837;