10-38054785-T-A

Variant names:

• chr10-38054785-T-A
• rs780179746
• NM_006954.2:c.661T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006954.2(ZNF33A):​c.661T>A​(p.Tyr221Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,396 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y221D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF33A NM_006954.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF33A	NM_006954.2	c.661T>A	p.Tyr221Asn	missense_variant	Exon 5 of 5	ENST00000432900.7	NP_008885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF33A	ENST00000432900.7	c.661T>A	p.Tyr221Asn	missense_variant	Exon 5 of 5	1	NM_006954.2	ENSP00000402467.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461396 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726990

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111922

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T;.;.;.;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.65	T;T;T;T;T
M_CAP	Benign	0.00096	T
MetaRNN	Uncertain	0.58	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	.;.;.;.;M
PhyloP100		0.21
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.6	.;.;.;.;D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	.;.;.;.;D
Sift4G	Uncertain	0.052	T;D;T;T;T
Polyphen		0.99	.;.;.;.;D
Vest4		0.47
MutPred		0.75		.;.;.;.;Gain of disorder (P = 0.0042);
MVP		0.28
MPC		0.17
ClinPred		0.91	D
GERP RS		2.3
Varity_R		0.30
gMVP		0.18
Mutation Taster		=97/3	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: rs780179746; hg19: chr10-38343713;