19-7081437-C-G

Variant names:

• chr19-7081437-C-G
• NM_024341.3:c.325C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024341.3(ZNF557):​c.325C>G​(p.Leu109Val) 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 1,460,922 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. L109I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF557 NM_024341.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049641043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF557	NM_024341.3	c.325C>G	p.Leu109Val	missense_variant	Exon 6 of 8	ENST00000252840.11	NP_077317.2
ZNF557	NM_001044387.2	c.325C>G	p.Leu109Val	missense_variant	Exon 6 of 8		NP_001037852.1
ZNF557	NM_001044388.2	c.304C>G	p.Leu102Val	missense_variant	Exon 6 of 8		NP_001037853.1
ZNF557	XM_047439432.1	c.304C>G	p.Leu102Val	missense_variant	Exon 6 of 8		XP_047295388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF557	ENST00000252840.11	c.325C>G	p.Leu109Val	missense_variant	Exon 6 of 8	1	NM_024341.3	ENSP00000252840.5
ZNF557	ENST00000414706.2	c.304C>G	p.Leu102Val	missense_variant	Exon 6 of 8	2		ENSP00000404065.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460922 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726754

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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.89
DEOGEN2	Benign	0.021	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00067	N
LIST_S2	Benign	0.0058	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.92	.;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.65	N;.
REVEL	Benign	0.011
Sift	Benign	0.52	T;.
Sift4G	Benign	0.54	T;T
Polyphen		0.0020	B;B
Vest4		0.13
MutPred		0.20		.;Gain of glycosylation at S103 (P = 0.1058);
MVP		0.16
MPC		0.32
ClinPred		0.022	T
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.036
gMVP		0.024

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: chr19-7081448;