chr19-7517763-T-C

Variant names:

• chr19-7517763-T-C
• rs661821
• NM_018083.5:c.-38-1442T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018083.5(ZNF358):​c.-38-1442T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,922 control chromosomes in the GnomAD database, including 28,518 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (28518 hom., cov: 30)
• Consequence: ZNF358 NM_018083.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

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.-38-1442T>C		intron	N/A	NP_060553.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF358	ENST00000597229.2	TSL:2 MANE Select	c.-38-1442T>C		intron	N/A	ENSP00000472305.1	Q9NW07
	ENSG00000267952	ENST00000599312.1	TSL:2	c.61-1442T>C		intron	N/A	ENSP00000469588.1	M0QY47
	ZNF358	ENST00000950346.1		c.-981T>C		5_prime_UTR	Exon 1 of 2	ENSP00000620405.1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92786 AN: 151804 Hom.: 28481 Cov.: 30

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.611 AC: 92871 AN: 151922 Hom.: 28518 Cov.: 30 AF XY: 0.611 AC XY: 45360 AN XY: 74262

African (AFR) AF: 0.579 AC: 23971 AN: 41418

American (AMR) AF: 0.690 AC: 10536 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2080 AN: 3472

East Asian (EAS) AF: 0.463 AC: 2388 AN: 5158

South Asian (SAS) AF: 0.577 AC: 2778 AN: 4812

European-Finnish (FIN) AF: 0.650 AC: 6873 AN: 10570

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42355 AN: 67918

Other (OTH) AF: 0.618 AC: 1298 AN: 2102

Alfa AF: 0.618 Hom.: 47627

Bravo AF: 0.612

Asia WGS AF: 0.594 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.78
PhyloP100		-0.030
Mutation Taster		=100/0	polymorphism (auto)

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: rs661821; hg19: chr19-7582649;