rs751657962

Variant names:

• chr19-7083083-A-C
• NM_024341.3:c.632A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-7083083-A-C
• chr19-7083083-A-G
• chr19-7083083-A-T

Variant summary

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

The NM_024341.3(ZNF557):​c.632A>C​(p.Asn211Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. N211D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF557 NM_024341.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=0.04841882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF557	NM_024341.3	c.632A>C	p.Asn211Thr	missense_variant	Exon 8 of 8	ENST00000252840.11	NP_077317.2
ZNF557	NM_001044387.2	c.632A>C	p.Asn211Thr	missense_variant	Exon 8 of 8		NP_001037852.1
ZNF557	NM_001044388.2	c.611A>C	p.Asn204Thr	missense_variant	Exon 8 of 8		NP_001037853.1
ZNF557	XM_047439432.1	c.611A>C	p.Asn204Thr	missense_variant	Exon 8 of 8		XP_047295388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF557	ENST00000252840.11	c.632A>C	p.Asn211Thr	missense_variant	Exon 8 of 8	1	NM_024341.3	ENSP00000252840.5
ZNF557	ENST00000414706.2	c.611A>C	p.Asn204Thr	missense_variant	Exon 8 of 8	2		ENSP00000404065.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461810 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727202

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.66
DEOGEN2	Benign	0.15	.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0	N
LIST_S2	Benign	0.081	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.36	.;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.3	D;.
REVEL	Benign	0.096
Sift	Benign	0.075	T;.
Sift4G	Benign	0.10	T;T
Polyphen		0.0060	B;B
Vest4		0.10
MutPred		0.27		.;Gain of phosphorylation at N204 (P = 0.0595);
MVP		0.12
MPC		0.068
ClinPred		0.049	T
GERP RS		-1.1
Varity_R		0.067
gMVP		0.023

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: chr19-7083094;