rs374154942

Variant names:

• chr19-7082919-G-T
• rs374154942
• NM_024341.3:c.468G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-7082919-G-T
• chr19-7082919-G-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.468G>T​(p.Gln156His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000498 in 1,606,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: ZNF557 NM_024341.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.52
• Publications: 1 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=0.13593677).

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.468G>T	p.Gln156His	missense	Exon 8 of 8	NP_077317.2	Q8N988-2
	ZNF557	NM_001044387.2		c.468G>T	p.Gln156His	missense	Exon 8 of 8	NP_001037852.1	Q8N988-2
	ZNF557	NM_001044388.2		c.447G>T	p.Gln149His	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.468G>T	p.Gln156His	missense	Exon 8 of 8	ENSP00000252840.5	Q8N988-2
	ZNF557	ENST00000882902.1		c.468G>T	p.Gln156His	missense	Exon 8 of 8	ENSP00000552961.1
	ZNF557	ENST00000882905.1		c.468G>T	p.Gln156His	missense	Exon 9 of 9	ENSP00000552964.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000244 AC: 6 AN: 245474 AF XY: 0.0000225

Gnomad AFR exome AF: 0.000129

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: 0.0000270

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000495 AC: 72 AN: 1454550 Hom.: 0 Cov.: 30 AF XY: 0.0000498 AC XY: 36 AN XY: 722850

African (AFR) AF: 0.00 AC: 0 AN: 33248

American (AMR) AF: 0.00 AC: 0 AN: 43872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25644

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 85384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.0000650 AC: 72 AN: 1107764

Other (OTH) AF: 0.00 AC: 0 AN: 60034

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74348

African (AFR) AF: 0.0000723 AC: 3 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15266

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.000231 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	0.25
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.0	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		-1.5
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.033
Sift	Benign	0.23	T
Sift4G	Benign	0.076	T
Polyphen		0.99	D
Vest4		0.10
MutPred		0.40		Gain of catalytic residue at Q149 (P = 0.0435)
MVP		0.39
MPC		0.34
ClinPred		0.18	T
GERP RS		1.3
Varity_R		0.16
gMVP		0.060
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs374154942; hg19: chr19-7082930;