19-7075672-C-T

Variant names:

• chr19-7075672-C-T
• NM_024341.3:c.49C>T

Variant summary

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

The NM_024341.3(ZNF557):​c.49C>T​(p.Pro17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF557 NM_024341.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.638
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059798658).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024341.3. 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
	ZNF557	NM_024341.3	MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 4 of 8	NP_077317.2	Q8N988-2
	ZNF557	NM_001044387.2		c.49C>T	p.Pro17Ser	missense	Exon 4 of 8	NP_001037852.1	Q8N988-2
	ZNF557	NM_001044388.2		c.32-4C>T		splice_region intron	N/A	NP_001037853.1	Q8N988-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF557	ENST00000252840.11	TSL:1 MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 4 of 8	ENSP00000252840.5	Q8N988-2
	ZNF557	ENST00000882902.1		c.49C>T	p.Pro17Ser	missense	Exon 4 of 8	ENSP00000552961.1
	ZNF557	ENST00000882905.1		c.49C>T	p.Pro17Ser	missense	Exon 5 of 9	ENSP00000552964.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Benign	0.093
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.30
DANN	Uncertain	0.99
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.64
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.0050
Sift	Benign	0.47	T
Sift4G	Benign	0.20	T
Polyphen		0.0020	B
Vest4		0.14
MVP		0.072
ClinPred		0.12	T
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.23
Mutation Taster		=98/2	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

hg19: chr19-7075683; COSMIC: COSV99422265;