chr19-7082945-C-A

Variant names:

• chr19-7082945-C-A
• rs554909679
• NM_024341.3:c.494C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024341.3(ZNF557):​c.494C>A​(p.Ser165Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF557 NM_024341.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.531
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17528102).

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.494C>A	p.Ser165Tyr	missense	Exon 8 of 8	NP_077317.2	Q8N988-2
	ZNF557	NM_001044387.2		c.494C>A	p.Ser165Tyr	missense	Exon 8 of 8	NP_001037852.1	Q8N988-2
	ZNF557	NM_001044388.2		c.473C>A	p.Ser158Tyr	missense	Exon 8 of 8	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.494C>A	p.Ser165Tyr	missense	Exon 8 of 8	ENSP00000252840.5	Q8N988-2
	ZNF557	ENST00000882902.1		c.494C>A	p.Ser165Tyr	missense	Exon 8 of 8	ENSP00000552961.1
	ZNF557	ENST00000882905.1		c.494C>A	p.Ser165Tyr	missense	Exon 9 of 9	ENSP00000552964.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248868 AF XY: 0.00000741

Gnomad AFR exome AF: 0.0000643

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: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460490 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726506

African (AFR) AF: 0.0000299 AC: 1 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111368

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152330 Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2 AN XY: 74488

African (AFR) AF: 0.000120 AC: 5 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.0	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.53
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.039
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.037	D
Polyphen		0.99	D
Vest4		0.25
MutPred		0.54		Loss of disorder (P = 0.0106)
MVP		0.34
MPC		0.41
ClinPred		0.94	D
GERP RS		0.16
Varity_R		0.28
gMVP		0.017
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

dbSNP: rs554909679; hg19: chr19-7082956;