10-37819248-C-T

Position:

• chr10-37819248-C-T

Variant summary

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

The ENST00000414066.1(TLK2P2):​n.1598G>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.456 in 850,566 control chromosomes in the GnomAD database, including 91,401 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 0.48 (17675 hom., cov: 32)
  • Exomes 𝑓: 0.45 (73726 hom.)
• Consequence: TLK2P2 ENST00000414066.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04

Genes affected

TLK2P2 (HGNC:22227): (tousled like kinase 2 pseudogene 2)

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF248	NM_001267607.3	c.330+13777G>A		intron_variant
ZNF248	NM_001352476.2	c.330+13777G>A		intron_variant
ZNF248	NM_001352477.2	c.*51+11984G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLK2P2	ENST00000414066.1	n.1598G>A		non_coding_transcript_exon_variant	2/2
ZNF248	ENST00000485560.5	c.330+13777G>A		intron_variant, NMD_transcript_variant		1
ZNF248	ENST00000615949.6	c.330+13777G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72502 AN: 151906 Hom.: 17634 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.452 AC: 315682 AN: 698538 Hom.: 73726 Cov.: 9 AF XY: 0.444 AC XY: 166571 AN XY: 375570

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.540

Gnomad4 ASJ exome AF: 0.418

Gnomad4 EAS exome AF: 0.529

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.332

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.478 AC: 72596 AN: 152028 Hom.: 17675 Cov.: 32 AF XY: 0.471 AC XY: 34952 AN XY: 74278

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.491

Alfa AF: 0.474 Hom.: 2131

Bravo AF: 0.501

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200910; hg19: chr10-38108176;