10-38040493-G-C

Variant names:

• chr10-38040493-G-C
• rs633400
• NM_006954.2:c.251-13882G>C

Variant summary

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

The NM_006954.2(ZNF33A):​c.251-13882G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,190 control chromosomes in the GnomAD database, including 58,623 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 0.88 (58623 hom., cov: 32)
• Consequence: ZNF33A NM_006954.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 2 publications found

Genes affected

ZNF33A (HGNC:13096): (zinc finger protein 33A) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006954.2. 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
	ZNF33A	NM_006954.2	MANE Select	c.251-13882G>C		intron	N/A	NP_008885.1	Q06730-2
	ZNF33A	NM_001278177.2		c.314-13882G>C		intron	N/A	NP_001265106.1
	ZNF33A	NM_001278173.1		c.305-13882G>C		intron	N/A	NP_001265102.1	A0A0A0MR11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF33A	ENST00000432900.7	TSL:1 MANE Select	c.251-13882G>C		intron	N/A	ENSP00000402467.3	Q06730-2
	ZNF33A	ENST00000458705.6	TSL:1	c.251-13885G>C		intron	N/A	ENSP00000387713.2	Q06730-1
	ZNF33A	ENST00000307441.13	TSL:4	c.305-13882G>C		intron	N/A	ENSP00000304268.10	A0A0A0MR11

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133309 AN: 152072 Hom.: 58565 Cov.: 32

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.859

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.877 AC: 133425 AN: 152190 Hom.: 58623 Cov.: 32 AF XY: 0.877 AC XY: 65250 AN XY: 74410

African (AFR) AF: 0.915 AC: 38019 AN: 41542

American (AMR) AF: 0.807 AC: 12332 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 2990 AN: 3472

East Asian (EAS) AF: 0.896 AC: 4640 AN: 5178

South Asian (SAS) AF: 0.936 AC: 4523 AN: 4830

European-Finnish (FIN) AF: 0.906 AC: 9584 AN: 10574

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58468 AN: 68000

Other (OTH) AF: 0.860 AC: 1819 AN: 2116

Alfa AF: 0.850 Hom.: 2565

Bravo AF: 0.867

Asia WGS AF: 0.917 AC: 3189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.24
DANN	Benign	0.23
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs633400; hg19: chr10-38329421;