chr5-43161235-A-G

Position:

• chr5-43161235-A-G

Variant summary

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

The NM_001330707.2(ZNF131):​c.372-14A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,576,526 control chromosomes in the GnomAD database, including 64,032 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6295 hom., cov: 32)
  • Exomes 𝑓: 0.27 (57737 hom.)
• Consequence: ZNF131 NM_001330707.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669

Genes affected

ZNF131 (HGNC:12915): (zinc finger protein 131) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor activity, RNA polymerase II-specific; and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Located in intermediate filament cytoskeleton and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF131	NM_001330707.2	c.372-14A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000682664.1	NP_001317636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF131	ENST00000682664.1	c.372-14A>G		splice_polypyrimidine_tract_variant, intron_variant			NM_001330707.2	ENSP00000507111	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41643 AN: 152030 Hom.: 6286 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.269

GnomAD3 exomes AF: 0.313 AC: 68775 AN: 219994 Hom.: 12220 AF XY: 0.306 AC XY: 36570 AN XY: 119574

Gnomad AFR exome AF: 0.239

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.646

Gnomad SAS exome AF: 0.337

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.285

GnomAD4 exome AF: 0.274 AC: 390923 AN: 1424378 Hom.: 57737 Cov.: 32 AF XY: 0.275 AC XY: 194061 AN XY: 706208

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.414

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.642

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.274 AC: 41674 AN: 152148 Hom.: 6295 Cov.: 32 AF XY: 0.279 AC XY: 20752 AN XY: 74404

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.271

Alfa AF: 0.253 Hom.: 933

Bravo AF: 0.282

Asia WGS AF: 0.473 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.29
DANN	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs903391; hg19: chr5-43161337; COSMIC: COSV61002651; COSMIC: COSV61002651;