10-37819248-C-T

Variant names:

• chr10-37819248-C-T
• rs200910
• ENST00000485560.5:n.330+13777G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000485560.5(ZNF248):​n.330+13777G>A variant causes a intron 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: ZNF248 ENST00000485560.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000485560.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF248	NM_001267607.3		c.330+13777G>A		intron	N/A	NP_001254536.1
	ZNF248	NM_001352476.2		c.330+13777G>A		intron	N/A	NP_001339405.1
	ZNF248	NM_001352477.2		c.*51+11984G>A		intron	N/A	NP_001339406.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF248	ENST00000485560.5	TSL:1	n.330+13777G>A		intron	N/A	ENSP00000473904.1
	TLK2P2	ENST00000414066.1	TSL:6	n.1598G>A		non_coding_transcript_exon	Exon 2 of 2
	ZNF248	ENST00000615949.6	TSL:5	c.330+13777G>A		intron	N/A	ENSP00000477940.1

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

African (AFR) AF: 0.520 AC: 9737 AN: 18722

American (AMR) AF: 0.540 AC: 22880 AN: 42382

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 8650 AN: 20686

East Asian (EAS) AF: 0.529 AC: 19065 AN: 36066

South Asian (SAS) AF: 0.289 AC: 20313 AN: 70174

European-Finnish (FIN) AF: 0.332 AC: 17141 AN: 51682

Middle Eastern (MID) AF: 0.468 AC: 1275 AN: 2724

European-Non Finnish (NFE) AF: 0.476 AC: 200561 AN: 421602

Other (OTH) AF: 0.466 AC: 16060 AN: 34500

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

African (AFR) AF: 0.522 AC: 21634 AN: 41472

American (AMR) AF: 0.521 AC: 7968 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1463 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2857 AN: 5160

South Asian (SAS) AF: 0.297 AC: 1430 AN: 4816

European-Finnish (FIN) AF: 0.317 AC: 3353 AN: 10572

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32260 AN: 67940

Other (OTH) AF: 0.491 AC: 1038 AN: 2114

Alfa AF: 0.476 Hom.: 2228

Bravo AF: 0.501

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.63
PhyloP100		4.0

Splicing

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

Other links and lift over

dbSNP: rs200910; hg19: chr10-38108176;