rs61742775

Variant names:

• chr19-7519443-C-G
• rs61742775
• NM_018083.5:c.201C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018083.5(ZNF358):​c.201C>G​(p.Val67Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00659 in 1,614,144 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (68 hom.)
• Consequence: ZNF358 NM_018083.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.176
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 19-7519443-C-G is Benign according to our data. Variant chr19-7519443-C-G is described in ClinVar as Benign. ClinVar VariationId is 782557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.176 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0137 (2084/152324) while in subpopulation AFR AF = 0.0369 (1534/41566). AF 95% confidence interval is 0.0354. There are 39 homozygotes in GnomAd4. There are 975 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 gene

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.201C>G	p.Val67Val	synonymous	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.201C>G	p.Val67Val	synonymous	Exon 2 of 2	ENSP00000472305.1	Q9NW07
	ENSG00000267952	ENST00000599312.1	TSL:2	c.*155C>G		3_prime_UTR	Exon 2 of 2	ENSP00000469588.1	M0QY47
	ZNF358	ENST00000908207.1		c.201C>G	p.Val67Val	synonymous	Exon 2 of 2	ENSP00000578266.1

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2083 AN: 152206 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00479

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00657 AC: 1650 AN: 251104 AF XY: 0.00590

Gnomad AFR exome AF: 0.0356

Gnomad AMR exome AF: 0.00451

Gnomad ASJ exome AF: 0.0235

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00116

Gnomad NFE exome AF: 0.00513

Gnomad OTH exome AF: 0.00800

GnomAD4 exome AF: 0.00585 AC: 8552 AN: 1461820 Hom.: 68 Cov.: 44 AF XY: 0.00564 AC XY: 4105 AN XY: 727204

African (AFR) AF: 0.0386 AC: 1292 AN: 33480

American (AMR) AF: 0.00490 AC: 219 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0232 AC: 607 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000742 AC: 64 AN: 86258

European-Finnish (FIN) AF: 0.00137 AC: 73 AN: 53348

Middle Eastern (MID) AF: 0.0257 AC: 148 AN: 5768

European-Non Finnish (NFE) AF: 0.00512 AC: 5699 AN: 1112010

Other (OTH) AF: 0.00743 AC: 449 AN: 60396

GnomAD4 genome AF: 0.0137 AC: 2084 AN: 152324 Hom.: 39 Cov.: 32 AF XY: 0.0131 AC XY: 975 AN XY: 74486

African (AFR) AF: 0.0369 AC: 1534 AN: 41566

American (AMR) AF: 0.00673 AC: 103 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10626

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00479 AC: 326 AN: 68030

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.00997 Hom.: 8

Bravo AF: 0.0158

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.00747

EpiControl AF: 0.00652

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.3
DANN	Benign	0.86
PhyloP100		-0.18
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: rs61742775; hg19: chr19-7584329;