chr19-14705169-C-T

Variant names:

• chr19-14705169-C-T
• rs149509478
• NM_032433.4:c.422C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001352241.2(ZNF333):​c.-271C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,612,172 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: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: ZNF333 NM_001352241.2 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.0001615
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.55
• Publications: 2 publications found

Genes affected

ZNF333 (HGNC:15624): (zinc finger protein 333) Predicted to enable DNA-binding transcription factor 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03718385).
• BP6: Variant 19-14705169-C-T is Benign according to our data. Variant chr19-14705169-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2404252.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352241.2. 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
	ZNF333	NM_032433.4	MANE Select	c.422C>T	p.Thr141Met	missense splice_region	Exon 6 of 12	NP_115809.1	Q96JL9-1
	ZNF333	NM_001352241.2		c.-271C>T		5_prime_UTR_premature_start_codon_gain	Exon 6 of 13	NP_001339170.1
	ZNF333	NM_001352243.2		c.-253C>T		5_prime_UTR_premature_start_codon_gain	Exon 6 of 12	NP_001339172.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF333	ENST00000292530.11	TSL:1 MANE Select	c.422C>T	p.Thr141Met	missense splice_region	Exon 6 of 12	ENSP00000292530.5	Q96JL9-1
	ZNF333	ENST00000540689.6	TSL:1	c.422C>T	p.Thr141Met	missense splice_region	Exon 6 of 12	ENSP00000438130.1	Q96JL9-3
	ZNF333	ENST00000597007.5	TSL:1	n.*415C>T		splice_region non_coding_transcript_exon	Exon 7 of 10	ENSP00000471574.1	M0R113

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 20 AN: 151992 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000140 AC: 35 AN: 250360 AF XY: 0.000155

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000937

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000205 AC: 299 AN: 1460180 Hom.: 0 Cov.: 31 AF XY: 0.000187 AC XY: 136 AN XY: 726410

African (AFR) AF: 0.0000897 AC: 3 AN: 33432

American (AMR) AF: 0.000157 AC: 7 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39658

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86162

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 53080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5450

European-Non Finnish (NFE) AF: 0.000227 AC: 252 AN: 1111352

Other (OTH) AF: 0.000133 AC: 8 AN: 60308

GnomAD4 genome AF: 0.000132 AC: 20 AN: 151992 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74204

African (AFR) AF: 0.0000483 AC: 2 AN: 41372

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.000193

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.93
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.00076	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-2.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.013
Sift	Benign	0.14	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.20
MVP		0.030
MPC		0.12
ClinPred		0.045	T
GERP RS		-3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.014
gMVP		0.35
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.11
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: rs149509478; hg19: chr19-14815981;