rs749209546

Variant names:

• chr19-57397132-C-G
• rs749209546
• NM_001172773.2:c.136C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-57397132-C-G
• chr19-57397132-C-T

Variant summary

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

The NM_001172773.2(ZNF548):​c.136C>G​(p.Arg46Gly) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R46C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF548 NM_001172773.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101030946).

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.136C>G	p.Arg46Gly	missense	Exon 3 of 4	NP_001166244.1	Q8NEK5-2
	ZNF548	NM_152909.4		c.100C>G	p.Arg34Gly	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.136C>G	p.Arg46Gly	missense	Exon 3 of 4	ENSP00000337555.6	Q8NEK5-2
	ZNF548	ENST00000366197.10	TSL:1	c.100C>G	p.Arg34Gly	missense	Exon 2 of 3	ENSP00000379482.3	Q8NEK5-1
	ENSG00000269533	ENST00000596400.1	TSL:4	c.51+2909C>G		intron	N/A	ENSP00000472277.1	M0R233

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.78
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.038	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-2.5
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.077
Sift	Benign	0.29	T
Sift4G	Benign	0.35	T
Polyphen		0.12	B
Vest4		0.23
MutPred		0.67		Loss of stability (P = 0.0339)
MVP		0.25
MPC		0.25
ClinPred		0.067	T
GERP RS		-3.7
Varity_R		0.15
gMVP		0.39
Mutation Taster		=98/2	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: rs749209546; hg19: chr19-57908500; COSMIC: COSV60242121;