NM_032453.2:c.901_902insTGTG

Variant names:

• chr19-37388950-C-CTGTG
• rs376931538
• NM_032453.2:c.901_902insTGTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_032453.2(ZNF527):​c.901_902insTGTG​(p.Pro301LeufsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,964 control chromosomes in the GnomAD database, including 16,493 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1181 hom., cov: 31)
  • Exomes 𝑓: 0.14 (15312 hom.)
• Consequence: ZNF527 NM_032453.2 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.11
• Publications: 10 publications found

Genes affected

ZNF527 (HGNC:29385): (zinc finger protein 527) 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-37388950-C-CTGTG is Benign according to our data. Variant chr19-37388950-C-CTGTG is described in ClinVar as Benign. ClinVar VariationId is 773354.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032453.2. 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
	ZNF527	NM_032453.2	MANE Select	c.901_902insTGTG	p.Pro301LeufsTer7	frameshift	Exon 5 of 5	NP_115829.1	Q8NB42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF527	ENST00000436120.7	TSL:4 MANE Select	c.901_902insTGTG	p.Pro301LeufsTer7	frameshift	Exon 5 of 5	ENSP00000390179.2	Q8NB42-1
	ZNF527	ENST00000969391.1		c.901_902insTGTG	p.Pro301LeufsTer7	frameshift	Exon 5 of 5	ENSP00000639450.1
	ZNF527	ENST00000587349.1	TSL:3	c.*5-3465_*5-3464insTGTG		intron	N/A	ENSP00000466096.1	K7ELI5

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16927 AN: 152016 Hom.: 1182 Cov.: 31

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0800

Gnomad SAS AF: 0.0785

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.0338 AC: 7504 AN: 222140 AF XY: 0.0373

Gnomad AFR exome AF: 0.00530

Gnomad AMR exome AF: 0.0118

Gnomad ASJ exome AF: 0.0516

Gnomad EAS exome AF: 0.0132

Gnomad FIN exome AF: 0.0320

Gnomad NFE exome AF: 0.0509

Gnomad OTH exome AF: 0.0277

GnomAD4 exome AF: 0.140 AC: 204755 AN: 1461830 Hom.: 15312 Cov.: 34 AF XY: 0.139 AC XY: 101279 AN XY: 727222

African (AFR) AF: 0.0258 AC: 865 AN: 33480

American (AMR) AF: 0.0738 AC: 3300 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3902 AN: 26134

East Asian (EAS) AF: 0.0777 AC: 3084 AN: 39700

South Asian (SAS) AF: 0.0851 AC: 7341 AN: 86254

European-Finnish (FIN) AF: 0.145 AC: 7736 AN: 53414

Middle Eastern (MID) AF: 0.106 AC: 609 AN: 5768

European-Non Finnish (NFE) AF: 0.153 AC: 169888 AN: 1111968

Other (OTH) AF: 0.133 AC: 8030 AN: 60392

GnomAD4 genome AF: 0.111 AC: 16918 AN: 152134 Hom.: 1181 Cov.: 31 AF XY: 0.109 AC XY: 8125 AN XY: 74388

African (AFR) AF: 0.0307 AC: 1276 AN: 41556

American (AMR) AF: 0.105 AC: 1598 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 539 AN: 3462

East Asian (EAS) AF: 0.0801 AC: 415 AN: 5178

South Asian (SAS) AF: 0.0784 AC: 378 AN: 4824

European-Finnish (FIN) AF: 0.136 AC: 1437 AN: 10592

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10906 AN: 67922

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.106 Hom.: 212

Bravo AF: 0.104

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=78/22	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs376931538; hg19: chr19-37879852; COSMIC: COSV62229307; COSMIC: COSV62229307;