rs193921000

Positions:

• chr16-30398874-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF48	NM_001214909.2	c.1624C>T	p.Pro542Ser	missense_variant	3/3	ENST00000613509.2	NP_001201838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF48	ENST00000613509.2	c.1624C>T	p.Pro542Ser	missense_variant	3/3	2	NM_001214909.2	ENSP00000480262.1
ZNF48	ENST00000320159.2	c.1624C>T	p.Pro542Ser	missense_variant	2/2	1		ENSP00000324056.2
ZNF48	ENST00000622647.3	c.1255C>T	p.Pro419Ser	missense_variant	2/2	4		ENSP00000479658.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.49	T;T;.
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.0	.;M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.0	.;.;D
REVEL	Benign	0.12
Sift	Benign	0.039	.;.;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		0.0	.;B;B
Vest4		0.11
MutPred		0.35		.;Gain of phosphorylation at P542 (P = 0.067);Gain of phosphorylation at P542 (P = 0.067);
MVP		0.43
MPC		0.40
ClinPred		0.32	T
GERP RS		2.5
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

Publications

LitVar

Other links and lift over

dbSNP: rs193921000; hg19: chr16-30410195; COSMIC: COSV60782614; COSMIC: COSV60782614;