chr19-57397169-C-T

Variant names:

• chr19-57397169-C-T
• NM_001172773.2:c.173C>T

Variant summary

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

The NM_001172773.2(ZNF548):​c.173C>T​(p.Ser58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF548 NM_001172773.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.158
• Publications: 0 publications found

Genes affected

ZNF548 (HGNC:26561): (zinc finger protein 548) 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]

ENSG00000269533 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172773.2. 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
	ZNF548	NM_001172773.2	MANE Select	c.173C>T	p.Ser58Leu	missense	Exon 3 of 4	NP_001166244.1	Q8NEK5-2
	ZNF548	NM_152909.4		c.137C>T	p.Ser46Leu	missense	Exon 2 of 3	NP_690873.2	Q8NEK5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF548	ENST00000336128.12	TSL:2 MANE Select	c.173C>T	p.Ser58Leu	missense	Exon 3 of 4	ENSP00000337555.6	Q8NEK5-2
	ZNF548	ENST00000366197.10	TSL:1	c.137C>T	p.Ser46Leu	missense	Exon 2 of 3	ENSP00000379482.3	Q8NEK5-1
	ENSG00000269533	ENST00000596400.1	TSL:4	c.51+2946C>T		intron	N/A	ENSP00000472277.1	M0R233

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.17
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0032	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.16
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.080
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.73		Loss of catalytic residue at S46 (P = 0.0107)
MVP		0.36
MPC		0.17
ClinPred		0.92	D
GERP RS		1.5
Varity_R		0.47
gMVP		0.29
Mutation Taster		=94/6	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

hg19: chr19-57908537; COSMIC: COSV100278278; COSMIC: COSV100278278;