rs752084

Variant names:

• chr19-48170687-G-A
• rs752084
• NM_199341.4:c.-37G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199341.4(ZSWIM9):​c.-37G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: ZSWIM9 NM_199341.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63

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]

LIG1 (HGNC:6598): (DNA ligase 1) This gene encodes a member of the ATP-dependent DNA ligase protein family. The encoded protein functions in DNA replication, recombination, and the base excision repair process. Mutations in this gene that lead to DNA ligase I deficiency result in immunodeficiency and increased sensitivity to DNA-damaging agents. Disruption of this gene may also be associated with a variety of cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM9	NM_199341.4	c.-37G>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000614654.2	NP_955373.3
ZSWIM9	XM_006723204.4	c.-270G>A		5_prime_UTR_variant	Exon 1 of 4		XP_006723267.1
ZSWIM9	XM_005259449.4	c.-679G>A		5_prime_UTR_variant	Exon 1 of 4		XP_005259506.1
ZSWIM9	XM_006723205.3	c.-33G>A		5_prime_UTR_variant	Exon 1 of 4		XP_006723268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM9	ENST00000614654	c.-37G>A		5_prime_UTR_variant	Exon 1 of 4	5	NM_199341.4	ENSP00000480314.1
ZSWIM9	ENST00000328759.11	c.-37G>A		upstream_gene_variant		1		ENSP00000331363.7
LIG1	ENST00000596549.6	c.-504C>T		upstream_gene_variant		4		ENSP00000471861.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.98

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs752084; hg19: chr19-48673944;