rs1122955

Positions:

• chr19-58434836-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003433.4(ZNF132):​c.608G>A​(p.Gly203Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,614,012 control chromosomes in the GnomAD database, including 33,666 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G203S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.17 (2535 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31131 hom.)
• Consequence: ZNF132 NM_003433.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.81

Genes affected

ZNF132 (HGNC:12916): (zinc finger protein 132) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF324B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052083135).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF132	NM_003433.4	c.608G>A	p.Gly203Asp	missense_variant	3/3	ENST00000254166.4
ZNF132	XM_047439361.1	c.569G>A	p.Gly190Asp	missense_variant	3/3
ZNF324B	XM_047438807.1	c.-5-4605C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF132	ENST00000254166.4	c.608G>A	p.Gly203Asp	missense_variant	3/3	1	NM_003433.4	P1
ZNF132	ENST00000599148.1	n.749G>A		non_coding_transcript_exon_variant	1/1
ZNF132	ENST00000703732.1	n.1074G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26404 AN: 152032 Hom.: 2534 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.159

GnomAD3 exomes AF: 0.182 AC: 45815 AN: 251374 Hom.: 4571 AF XY: 0.189 AC XY: 25723 AN XY: 135874

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.0635

Gnomad SAS exome AF: 0.189

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.215

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.202 AC: 295864 AN: 1461862 Hom.: 31131 Cov.: 36 AF XY: 0.204 AC XY: 148176 AN XY: 727238

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.0523

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.174 AC: 26424 AN: 152150 Hom.: 2535 Cov.: 32 AF XY: 0.171 AC XY: 12748 AN XY: 74374

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0608

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.160

Alfa AF: 0.201 Hom.: 6810

Bravo AF: 0.165

TwinsUK AF: 0.217 AC: 804

ALSPAC AF: 0.209 AC: 807

ESP6500AA AF: 0.108 AC: 477

ESP6500EA AF: 0.205 AC: 1761

ExAC AF: 0.184 AC: 22374

Asia WGS AF: 0.123 AC: 428 AN: 3478

EpiCase AF: 0.214

EpiControl AF: 0.214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0050
DANN	Benign	0.27
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00043	N
LIST_S2	Benign	0.019	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.36	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.010
Sift	Benign	1.0	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.022
MPC		0.013
ClinPred		0.00080	T
GERP RS		0.23
Varity_R		0.037
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1122955; hg19: chr19-58946203; COSMIC: COSV54235016; COSMIC: COSV54235016;