NM_001367834.3:c.49G>A

Variant names:

• chr19-13795697-G-A
• NM_001367834.3:c.49G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367834.3(ZSWIM4):​c.49G>A​(p.Glu17Lys) variant causes a missense 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZSWIM4 NM_001367834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

Genes affected

ZSWIM4 (HGNC:25704): (zinc finger SWIM-type containing 4) Predicted to enable zinc ion binding activity. Predicted to be part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08797404).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367834.3. 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
	ZSWIM4	NM_001367834.3	MANE Select	c.49G>A	p.Glu17Lys	missense	Exon 1 of 14	NP_001354763.1	K7ERJ6
	ZSWIM4	NM_023072.3		c.49G>A	p.Glu17Lys	missense	Exon 1 of 13	NP_075560.2	Q9H7M6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM4	ENST00000590508.6	TSL:2 MANE Select	c.49G>A	p.Glu17Lys	missense	Exon 1 of 14	ENSP00000468285.2	K7ERJ6
	ZSWIM4	ENST00000938264.1		c.49G>A	p.Glu17Lys	missense	Exon 1 of 15	ENSP00000608323.1
	ZSWIM4	ENST00000938266.1		c.49G>A	p.Glu17Lys	missense	Exon 1 of 14	ENSP00000608325.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 990604 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 469484

African (AFR) AF: 0.00 AC: 0 AN: 20656

American (AMR) AF: 0.00 AC: 0 AN: 7430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12620

East Asian (EAS) AF: 0.00 AC: 0 AN: 24020

South Asian (SAS) AF: 0.00 AC: 0 AN: 18060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 845284

Other (OTH) AF: 0.00 AC: 0 AN: 39472

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.035
Sift	Benign	0.11	T
Sift4G	Benign	0.74	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.27		Gain of MoRF binding (P = 9e-04)
MVP		0.15
MPC		0.67
ClinPred		0.11	T
GERP RS		0.81
PromoterAI		-0.036	Neutral
Varity_R		0.12
gMVP		0.28
Mutation Taster		=95/5	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

hg19: chr19-13906511;