16-30397768-C-A

Variant names:

• chr16-30397768-C-A
• rs148541483
• NM_001214909.2:c.518C>A

Variant summary

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

The NM_001214909.2(ZNF48):​c.518C>A​(p.Pro173Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: ZNF48 NM_001214909.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.859
• Publications: 0 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=0.013294101).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001214909.2. 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
	ZNF48	NM_001214909.2	MANE Select	c.518C>A	p.Pro173Gln	missense	Exon 3 of 3	NP_001201838.1	Q96MX3
	ZNF48	NM_001214906.1		c.518C>A	p.Pro173Gln	missense	Exon 3 of 3	NP_001201835.1	Q96MX3
	ZNF48	NM_152652.3		c.518C>A	p.Pro173Gln	missense	Exon 2 of 2	NP_689865.2	Q96MX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF48	ENST00000613509.2	TSL:2 MANE Select	c.518C>A	p.Pro173Gln	missense	Exon 3 of 3	ENSP00000480262.1	Q96MX3
	ZNF48	ENST00000320159.2	TSL:1	c.518C>A	p.Pro173Gln	missense	Exon 2 of 2	ENSP00000324056.2	Q96MX3
	ZNF48	ENST00000872220.1		c.518C>A	p.Pro173Gln	missense	Exon 3 of 3	ENSP00000542279.1

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152004 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000943

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000679 AC: 17 AN: 250256 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00107

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461652 Hom.: 0 Cov.: 82 AF XY: 0.0000206 AC XY: 15 AN XY: 727130

African (AFR) AF: 0.000836 AC: 28 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53182

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.000116 AC: 7 AN: 60394

GnomAD4 genome AF: 0.000296 AC: 45 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74376

African (AFR) AF: 0.00101 AC: 42 AN: 41484

American (AMR) AF: 0.000131 AC: 2 AN: 15266

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000212 Hom.: 0

Bravo AF: 0.000382

ESP6500AA AF: 0.00137 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000107 AC: 13

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	0.11
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.95	N
PhyloP100		0.86
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.028
Sift	Benign	0.093	T
Sift4G	Benign	0.17	T
Polyphen		0.0030	B
Vest4		0.22
MVP		0.29
MPC		0.37
ClinPred		0.0074	T
GERP RS		1.9
Varity_R		0.035
gMVP		0.26
Mutation Taster		=96/4	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: rs148541483; hg19: chr16-30409089; COSMIC: COSV107331892; COSMIC: COSV107331892;