rs1322319

Variant names:

• chr10-37856581-A-G
• rs1322319
• ENST00000611278.4:c.-271T>C

Variant summary

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

The NM_001352472.2(ZNF248):​c.-271T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,142,014 control chromosomes in the GnomAD database, including 11,443 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 0.13 (1353 hom., cov: 32)
  • Exomes 𝑓: 0.14 (10090 hom.)
• Consequence: ZNF248 NM_001352472.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352472.2. 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
	ZNF248	NM_021045.3	MANE Select	c.-125-49T>C		intron	N/A	NP_066383.1	A2RUI7
	ZNF248	NM_001352472.2		c.-271T>C		5_prime_UTR	Exon 1 of 4	NP_001339401.1	Q8NDW4-1
	ZNF248	NM_001352492.2		c.-680T>C		5_prime_UTR	Exon 1 of 6	NP_001339421.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF248	ENST00000611278.4	TSL:1	c.-271T>C		5_prime_UTR	Exon 1 of 5	ENSP00000484191.1	Q8NDW4-2
	ZNF248	ENST00000395867.8	TSL:1 MANE Select	c.-125-49T>C		intron	N/A	ENSP00000379208.3	Q8NDW4-1
	ZNF248	ENST00000374648.7	TSL:1	c.-125-49T>C		intron	N/A	ENSP00000363778.3	Q8NDW4-2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19539 AN: 151950 Hom.: 1352 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.141 AC: 139190 AN: 989946 Hom.: 10090 Cov.: 29 AF XY: 0.141 AC XY: 65422 AN XY: 465050

African (AFR) AF: 0.0927 AC: 1960 AN: 21144

American (AMR) AF: 0.189 AC: 1256 AN: 6652

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 1542 AN: 11482

East Asian (EAS) AF: 0.103 AC: 1844 AN: 17854

South Asian (SAS) AF: 0.0656 AC: 1305 AN: 19898

European-Finnish (FIN) AF: 0.0760 AC: 729 AN: 9590

Middle Eastern (MID) AF: 0.144 AC: 347 AN: 2406

European-Non Finnish (NFE) AF: 0.145 AC: 125273 AN: 863282

Other (OTH) AF: 0.131 AC: 4934 AN: 37638

GnomAD4 genome AF: 0.129 AC: 19544 AN: 152068 Hom.: 1353 Cov.: 32 AF XY: 0.128 AC XY: 9521 AN XY: 74318

African (AFR) AF: 0.104 AC: 4298 AN: 41494

American (AMR) AF: 0.195 AC: 2976 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3472

East Asian (EAS) AF: 0.103 AC: 532 AN: 5152

South Asian (SAS) AF: 0.0624 AC: 301 AN: 4822

European-Finnish (FIN) AF: 0.0916 AC: 967 AN: 10554

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9524 AN: 67988

Other (OTH) AF: 0.143 AC: 300 AN: 2104

Alfa AF: 0.131 Hom.: 163

Bravo AF: 0.139

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1322319; hg19: chr10-38145509;