rs193921000

Variant names:

• chr16-30398874-C-T
• rs193921000
• NM_001214909.2:c.1624C>T
• ZNF48 p.Pro542Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001214909.2(ZNF48):​c.1624C>T​(p.Pro542Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF48 NM_001214909.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.05
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1698443).

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.1624C>T	p.Pro542Ser	missense	Exon 3 of 3	NP_001201838.1	Q96MX3
	ZNF48	NM_001214906.1		c.1624C>T	p.Pro542Ser	missense	Exon 3 of 3	NP_001201835.1	Q96MX3
	ZNF48	NM_152652.3		c.1624C>T	p.Pro542Ser	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.1624C>T	p.Pro542Ser	missense	Exon 3 of 3	ENSP00000480262.1	Q96MX3
	ZNF48	ENST00000320159.2	TSL:1	c.1624C>T	p.Pro542Ser	missense	Exon 2 of 2	ENSP00000324056.2	Q96MX3
	ZNF48	ENST00000872220.1		c.1624C>T	p.Pro542Ser	missense	Exon 3 of 3	ENSP00000542279.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.12
Sift	Benign	0.039	D
Sift4G	Uncertain	0.018	D
Varity_R		0.11
gMVP		0.60

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs193921000;

hg19: chr16-30410195;

COSMIC: COSV60782614;

COSMIC: COSV60782614;