rs1148274

Positions:

• chr10-37818988-T-G

Variant summary

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

The NM_001267607.3(ZNF248):​c.330+14037A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 1,000,562 control chromosomes in the GnomAD database, including 3,205 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 0.060 (351 hom., cov: 32)
  • Exomes 𝑓: 0.074 (2854 hom.)
• Consequence: ZNF248 NM_001267607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701

Genes affected

ZNF248 (HGNC:13041): (zinc finger protein 248) 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]

TLK2P2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF248	NM_001267607.3	c.330+14037A>C		intron_variant			NP_001254536.1
ZNF248	NM_001352476.2	c.330+14037A>C		intron_variant			NP_001339405.1
ZNF248	NM_001352477.2	c.*51+12244A>C		intron_variant			NP_001339406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF248	ENST00000485560.5	n.330+14037A>C		intron_variant		1		ENSP00000473904.1
ZNF248	ENST00000615949.6	c.330+14037A>C		intron_variant		5		ENSP00000477940.1
TLK2P2	ENST00000414066.1	n.1858A>C		non_coding_transcript_exon_variant	2/2	6

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9117 AN: 152102 Hom.: 350 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0663

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.0718

GnomAD4 exome AF: 0.0743 AC: 63073 AN: 848342 Hom.: 2854 Cov.: 12 AF XY: 0.0725 AC XY: 32340 AN XY: 445784

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.0496

Gnomad4 ASJ exome AF: 0.0847

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0127

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.0912

Gnomad4 OTH exome AF: 0.0742

GnomAD4 genome AF: 0.0599 AC: 9119 AN: 152220 Hom.: 351 Cov.: 32 AF XY: 0.0569 AC XY: 4238 AN XY: 74420

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0642

Gnomad4 ASJ AF: 0.0845

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.0663

Gnomad4 NFE AF: 0.0896

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.0788 Hom.: 233

Bravo AF: 0.0590

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.4
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1148274; hg19: chr10-38107916;