chr19-57590352-C-G

Variant names:

• chr19-57590352-C-G
• rs753153477
• NM_001010879.4:c.541C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010879.4(ZIK1):​c.541C>G​(p.Arg181Gly) 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. 16/22 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. R181W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZIK1 NM_001010879.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 0 publications found

Genes affected

ZIK1 (HGNC:33104): (zinc finger protein interacting with K protein 1) 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]

ENSG00000303240 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038844913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010879.4. 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
	ZIK1	NM_001010879.4	MANE Select	c.541C>G	p.Arg181Gly	missense	Exon 4 of 4	NP_001010879.2	Q3SY52-1
	ZIK1	NM_001321145.2		c.502C>G	p.Arg168Gly	missense	Exon 3 of 3	NP_001308074.1	F5H435
	ZIK1	NM_001321146.2		c.376C>G	p.Arg126Gly	missense	Exon 3 of 3	NP_001308075.1	Q3SY52-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIK1	ENST00000597850.2	TSL:1 MANE Select	c.541C>G	p.Arg181Gly	missense	Exon 4 of 4	ENSP00000472867.1	Q3SY52-1
	ZIK1	ENST00000599456.1	TSL:1	c.376C>G	p.Arg126Gly	missense	Exon 3 of 3	ENSP00000468937.1	Q3SY52-2
	ZIK1	ENST00000307468.4	TSL:1	c.*285C>G		3_prime_UTR	Exon 2 of 2	ENSP00000303820.4	X6R413

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.24
DANN	Benign	0.11
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00066	N
LIST_S2	Benign	0.047	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.57	N
PhyloP100		0.12
PrimateAI	Benign	0.21	T
PROVEAN	Benign	3.8	N
REVEL	Benign	0.030
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.048
MutPred		0.44		Loss of MoRF binding (P = 0.0103)
MVP		0.081
MPC		0.20
ClinPred		0.044	T
GERP RS		0.69
Varity_R		0.047
gMVP		0.11
Mutation Taster		=100/0	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: rs753153477; hg19: chr19-58101720;