rs661821

Positions:

• chr19-7517763-T-C
• chr19-7517763-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105372261 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF358	NM_018083.5	c.-38-1442T>C		intron_variant		ENST00000597229.2	NP_060553.4
LOC105372261	XR_936294.3	n.937-3288A>G		intron_variant, non_coding_transcript_variant
ZNF358	XM_005272460.4	c.-38-1442T>C		intron_variant			XP_005272517.1
ZNF358	XM_047438181.1	c.20-1442T>C		intron_variant			XP_047294137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF358	ENST00000597229.2	c.-38-1442T>C		intron_variant		2	NM_018083.5	ENSP00000472305	P1
ZNF358	ENST00000596712.1	c.-38-1442T>C		intron_variant		3		ENSP00000472777

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

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.618

Alfa AF: 0.616 Hom.: 37220

Bravo AF: 0.612

Asia WGS AF: 0.594 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs661821; hg19: chr19-7582649;