19-7075096-C-T

Variant names:

• chr19-7075096-C-T
• rs746659003
• NM_024341.3:c.22C>T

Variant summary

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

The NM_024341.3(ZNF557):​c.22C>T​(p.Pro8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,852 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. P8A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: ZNF557 NM_024341.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

Genes affected

ZNF557 (HGNC:28632): (zinc finger protein 557) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be 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=0.07380536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF557	NM_024341.3	c.22C>T	p.Pro8Ser	missense_variant	Exon 3 of 8	ENST00000252840.11	NP_077317.2
ZNF557	NM_001044387.2	c.22C>T	p.Pro8Ser	missense_variant	Exon 3 of 8		NP_001037852.1
ZNF557	NM_001044388.2	c.22C>T	p.Pro8Ser	missense_variant	Exon 3 of 8		NP_001037853.1
ZNF557	XM_047439432.1	c.22C>T	p.Pro8Ser	missense_variant	Exon 3 of 8		XP_047295388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF557	ENST00000252840.11	c.22C>T	p.Pro8Ser	missense_variant	Exon 3 of 8	1	NM_024341.3	ENSP00000252840.5
ZNF557	ENST00000414706.2	c.22C>T	p.Pro8Ser	missense_variant	Exon 3 of 8	2		ENSP00000404065.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727226

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: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.9
DANN	Benign	0.40
DEOGEN2	Benign	0.014	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.0090
Sift	Benign	0.46	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.10	B;B
Vest4		0.18
MutPred		0.38		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.12
MPC		0.084
ClinPred		0.015	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.017
gMVP		0.28

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: rs746659003; hg19: chr19-7075107;