chr16-30397521-C-T

Variant names:

• chr16-30397521-C-T
• rs141193628
• NM_001214909.2:c.271C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001214907.1(ZNF48):​c.-99C>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 0.000366 in 1,614,016 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: ZNF48 NM_001214907.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65
• Publications: 4 publications found

Genes affected

ZNF48 (HGNC:13114): (zinc finger protein 48) Enables identical protein 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.063230515).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001214907.1. 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
	ZNF48	NM_001214909.2	MANE Select	c.271C>T	p.Arg91Trp	missense	Exon 3 of 3	NP_001201838.1	Q96MX3
	ZNF48	NM_001214907.1		c.-99C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 2	NP_001201836.1	A0A087WVT1
	ZNF48	NM_001324494.2		c.-99C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 2	NP_001311423.1	A0A087WVT1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF48	ENST00000613509.2	TSL:2 MANE Select	c.271C>T	p.Arg91Trp	missense	Exon 3 of 3	ENSP00000480262.1	Q96MX3
	ZNF48	ENST00000320159.2	TSL:1	c.271C>T	p.Arg91Trp	missense	Exon 2 of 2	ENSP00000324056.2	Q96MX3
	ZNF48	ENST00000622647.3	TSL:4	c.-99C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 2	ENSP00000479658.1	A0A087WVT1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000275 AC: 69 AN: 251348 AF XY: 0.000280

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.000405

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000384 AC: 561 AN: 1461834 Hom.: 0 Cov.: 86 AF XY: 0.000371 AC XY: 270 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.000674 AC: 36 AN: 53376

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

European-Non Finnish (NFE) AF: 0.000448 AC: 498 AN: 1112000

Other (OTH) AF: 0.000248 AC: 15 AN: 60394

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74340

African (AFR) AF: 0.000121 AC: 5 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68028

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000301 Hom.: 0

Bravo AF: 0.000227

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000272 AC: 33

EpiCase AF: 0.000164

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.15
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.058
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.026	D
Polyphen		0.92	P
Vest4		0.27
MVP		0.41
MPC		0.43
ClinPred		0.036	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.098
gMVP		0.35
Mutation Taster		=82/18	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: rs141193628; hg19: chr16-30408842;