rs201768786

Variant names:

• chr19-2917271-C-G
• NM_173480.3:c.650C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-2917271-C-G
• chr19-2917271-C-T

Variant summary

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

The NM_173480.3(ZNF57):​c.650C>G​(p.Thr217Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T217I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF57 NM_173480.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

Genes affected

ZNF57 (HGNC:13125): (zinc finger protein 57) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253392 (HGNC:):

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=0.086603165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF57	NM_173480.3	c.650C>G	p.Thr217Ser	missense_variant	Exon 4 of 4	ENST00000306908.10	NP_775751.1
ZNF57	NM_001319083.2	c.554C>G	p.Thr185Ser	missense_variant	Exon 4 of 4		NP_001306012.1
ZNF57	XM_011527682.3	c.554C>G	p.Thr185Ser	missense_variant	Exon 4 of 4		XP_011525984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF57	ENST00000306908.10	c.650C>G	p.Thr217Ser	missense_variant	Exon 4 of 4	1	NM_173480.3	ENSP00000303696.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461776 Hom.: 0 Cov.: 79 AF XY: 0.00000413 AC XY: 3 AN XY: 727170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.036
DANN	Benign	0.87
DEOGEN2	Benign	0.0031	.;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.36	T;T;T
M_CAP	Benign	0.00084	T
MetaRNN	Benign	0.087	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	.;N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	.;N;N
REVEL	Benign	0.017
Sift	Benign	0.16	.;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.15	.;B;.
Vest4		0.039
MutPred		0.47		.;Loss of glycosylation at T217 (P = 0.0547);.;
MVP		0.22
MPC		0.030
ClinPred		0.080	T
GERP RS		-4.7
Varity_R		0.020
gMVP		0.0093

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: chr19-2917269;