chr12-133202643-C-T

Variant names:

• chr12-133202643-C-T
• rs746814708
• NM_003415.3:c.957C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_003415.3(ZNF268):​c.957C>T​(p.Leu319Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000351 in 1,452,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: ZNF268 NM_003415.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.84
• Publications: 0 publications found

Genes affected

ZNF268 (HGNC:13061): (zinc finger protein 268) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including positive regulation of NIK/NF-kappaB signaling; positive regulation of nitrogen compound metabolic process; and regulation of apoptotic process. Located in actin cytoskeleton; cytosol; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-133202643-C-T is Benign according to our data. Variant chr12-133202643-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2643662.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.84 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003415.3. 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
	ZNF268	NM_003415.3	MANE Select	c.957C>T	p.Leu319Leu	synonymous	Exon 6 of 6	NP_003406.1	Q14587-1
	ZNF268	NM_001165881.3		c.957C>T	p.Leu319Leu	synonymous	Exon 6 of 6	NP_001159353.1	Q14587-1
	ZNF268	NM_001165882.3		c.708C>T	p.Leu236Leu	synonymous	Exon 6 of 6	NP_001159354.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF268	ENST00000536435.7	TSL:1 MANE Select	c.957C>T	p.Leu319Leu	synonymous	Exon 6 of 6	ENSP00000444412.3	Q14587-1
	ZNF268	ENST00000228289.9	TSL:1	c.957C>T	p.Leu319Leu	synonymous	Exon 6 of 6	ENSP00000228289.5	Q14587-1
	ZNF268	ENST00000541009.6	TSL:1	c.*481C>T		3_prime_UTR	Exon 7 of 7	ENSP00000439539.2	A0A075B6T9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000256 AC: 6 AN: 234442 AF XY: 0.0000315

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000382

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000351 AC: 51 AN: 1452980 Hom.: 0 Cov.: 34 AF XY: 0.0000471 AC XY: 34 AN XY: 722106

African (AFR) AF: 0.00 AC: 0 AN: 33350

American (AMR) AF: 0.00 AC: 0 AN: 42900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25808

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.000129 AC: 11 AN: 85272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52978

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5756

European-Non Finnish (NFE) AF: 0.0000271 AC: 30 AN: 1107354

Other (OTH) AF: 0.0000499 AC: 3 AN: 60092

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000833 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.52
PhyloP100		-4.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs746814708; hg19: chr12-133779229;