rs3730836

chr19-48171106-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_199341.4(ZSWIM9):c.-10+392A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 364,280 control chromosomes in the GnomAD database, including 44 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 0.011 (31 hom., cov: 32)
  • Exomes 𝑓: 0.010 (13 hom.)
• Consequence: ZSWIM9 NM_199341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

Genes affected

ZSWIM9 (HGNC:34495): (zinc finger SWIM-type containing 9) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0108 (1642/152272) while in subpopulation SAS AF= 0.0261 (126/4820). AF 95% confidence interval is 0.0224. There are 31 homozygotes in gnomad4. There are 797 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 30 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSWIM9	NM_199341.4	c.-10+392A>T		intron_variant		ENST00000614654.2
ZSWIM9	XM_005259449.4	c.-260A>T		5_prime_UTR_variant	1/4
ZSWIM9	XM_006723204.4	c.72+78A>T		intron_variant
ZSWIM9	XM_006723205.3	c.-10+396A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSWIM9	ENST00000614654.2	c.-10+392A>T		intron_variant		5	NM_199341.4	P2
ZSWIM9	ENST00000328759.11	c.-10+392A>T		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1640 AN: 152154 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00509

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.0105 AC: 2224 AN: 212008 Hom.: 13 AF XY: 0.0100 AC XY: 1007 AN XY: 100218

Gnomad4 AFR exome AF: 0.00549

Gnomad4 AMR exome AF: 0.0164

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.00347

Gnomad4 SAS exome AF: 0.0299

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0101

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.0108 AC: 1642 AN: 152272 Hom.: 31 Cov.: 32 AF XY: 0.0107 AC XY: 797 AN XY: 74458

Gnomad4 AFR AF: 0.00510

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.0185

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.0261

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0121

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00889 Hom.: 2

Bravo AF: 0.0117

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.2
Dann	Benign	0.74

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: rs3730836; hg19: chr19-48674363;