rs61735159

Variant names:

• chrX-137567552-G-A
• rs61735159
• NM_003413.4:c.861G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-137567552-G-A
• chrX-137567552-G-T

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_003413.4(ZIC3):​c.861G>A​(p.Val287Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,211,024 control chromosomes in the GnomAD database, including 10 homozygotes. There are 478 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0072 (4 hom., 216 hem., cov: 25)
  • Exomes 𝑓: 0.00084 (6 hom. 262 hem.)
• Consequence: ZIC3 NM_003413.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.08
• Publications: 1 publications found

Genes affected

ZIC3 (HGNC:12874): (Zic family member 3) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy, which includes congenital heart disease and left-right axis defects in organs. [provided by RefSeq, Jul 2008]

LINC02931 (HGNC:55853): (long intergenic non-protein coding RNA 2931)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant X-137567552-G-A is Benign according to our data. Variant chrX-137567552-G-A is described in ClinVar as Benign. ClinVar VariationId is 137959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.08 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0072 (812/112805) while in subpopulation AFR AF = 0.0253 (786/31123). AF 95% confidence interval is 0.0238. There are 4 homozygotes in GnomAd4. There are 216 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003413.4. 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
	ZIC3	NM_003413.4	MANE Select	c.861G>A	p.Val287Val	synonymous	Exon 1 of 3	NP_003404.1	O60481-1
	ZIC3	NM_001330661.1		c.861G>A	p.Val287Val	synonymous	Exon 1 of 3	NP_001317590.1	O60481-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIC3	ENST00000287538.10	TSL:1 MANE Select	c.861G>A	p.Val287Val	synonymous	Exon 1 of 3	ENSP00000287538.5	O60481-1
	ZIC3	ENST00000919832.1		c.861G>A	p.Val287Val	synonymous	Exon 4 of 6	ENSP00000589891.1
	ZIC3	ENST00000919833.1		c.861G>A	p.Val287Val	synonymous	Exon 4 of 6	ENSP00000589892.1

Frequencies

GnomAD3 genomes AF: 0.00720 AC: 812 AN: 112757 Hom.: 4 Cov.: 25

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00139

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000364

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.0000563

Gnomad OTH AF: 0.00394

GnomAD2 exomes AF: 0.00197 AC: 362 AN: 183312 AF XY: 0.00125

Gnomad AFR exome AF: 0.0257

Gnomad AMR exome AF: 0.000620

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000367

Gnomad OTH exome AF: 0.000884

GnomAD4 exome AF: 0.000840 AC: 923 AN: 1098219 Hom.: 6 Cov.: 33 AF XY: 0.000721 AC XY: 262 AN XY: 363581

African (AFR) AF: 0.0303 AC: 801 AN: 26402

American (AMR) AF: 0.000909 AC: 32 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54149

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40502

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4136

European-Non Finnish (NFE) AF: 0.0000166 AC: 14 AN: 842134

Other (OTH) AF: 0.00163 AC: 75 AN: 46098

GnomAD4 genome AF: 0.00720 AC: 812 AN: 112805 Hom.: 4 Cov.: 25 AF XY: 0.00618 AC XY: 216 AN XY: 34961

African (AFR) AF: 0.0253 AC: 786 AN: 31123

American (AMR) AF: 0.00139 AC: 15 AN: 10793

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3546

South Asian (SAS) AF: 0.000365 AC: 1 AN: 2741

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6198

Middle Eastern (MID) AF: 0.00457 AC: 1 AN: 219

European-Non Finnish (NFE) AF: 0.0000563 AC: 3 AN: 53298

Other (OTH) AF: 0.00389 AC: 6 AN: 1543

Alfa AF: 0.000921 Hom.: 6

Bravo AF: 0.00839

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Heterotaxy, visceral, 1, X-linked (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.5
DANN	Benign	0.92
PhyloP100		1.1
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: rs61735159; hg19: chrX-136649711;