19-7519271-C-A

Variant names:

• chr19-7519271-C-A
• rs372789030
• NM_018083.5:c.29C>A

Variant summary

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

The NM_018083.5(ZNF358):​c.29C>A​(p.Pro10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P10A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ZNF358 NM_018083.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 1 publications found

Genes affected

ZNF358 (HGNC:16838): (zinc finger protein 358) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in several processes, including embryonic forelimb morphogenesis; neural tube development; and stem cell population maintenance. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267952 (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=0.15568894).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018083.5. 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
	ZNF358	NM_018083.5	MANE Select	c.29C>A	p.Pro10Gln	missense	Exon 2 of 2	NP_060553.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF358	ENST00000597229.2	TSL:2 MANE Select	c.29C>A	p.Pro10Gln	missense	Exon 2 of 2	ENSP00000472305.1	Q9NW07
	ENSG00000267952	ENST00000599312.1	TSL:2	c.127C>A	p.Gln43Lys	missense	Exon 2 of 2	ENSP00000469588.1	M0QY47
	ZNF358	ENST00000908207.1		c.29C>A	p.Pro10Gln	missense	Exon 2 of 2	ENSP00000578266.1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 152016 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249426 AF XY: 0.00

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461810 Hom.: 0 Cov.: 36 AF XY: 0.00000275 AC XY: 2 AN XY: 727214

African (AFR) AF: 0.000179 AC: 6 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.0000724 AC: 11 AN: 152016 Hom.: 0 Cov.: 31 AF XY: 0.0000539 AC XY: 4 AN XY: 74244

African (AFR) AF: 0.000193 AC: 8 AN: 41384

American (AMR) AF: 0.000197 AC: 3 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000660 Hom.: 0

Bravo AF: 0.0000642

ESP6500AA AF: 0.000232 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0041	T
Eigen	Benign	0.073
Eigen_PC	Benign	0.059
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.20
PrimateAI	Uncertain	0.64	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.39
MVP		0.44
ClinPred		0.43	T
GERP RS		3.7
Varity_R		0.053
gMVP		0.26
Mutation Taster		=92/8	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: rs372789030; hg19: chr19-7584157;