rs199608753

Variant names:

• chr1-45020071-T-C
• NM_020883.2:c.2690A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-45020071-T-C
• chr1-45020071-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020883.2(ZSWIM5):​c.2690A>G​(p.Glu897Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E897A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZSWIM5 NM_020883.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.82

Genes affected

ZSWIM5 (HGNC:29299): (zinc finger SWIM-type containing 5) Predicted to enable zinc ion binding activity. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM5	NM_020883.2	c.2690A>G	p.Glu897Gly	missense_variant	Exon 13 of 14	ENST00000359600.6	NP_065934.1
ZSWIM5	XM_047426192.1	c.2513A>G	p.Glu838Gly	missense_variant	Exon 12 of 13		XP_047282148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM5	ENST00000359600.6	c.2690A>G	p.Glu897Gly	missense_variant	Exon 13 of 14	1	NM_020883.2	ENSP00000352614.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461476 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.077	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.69		Gain of MoRF binding (P = 0.0466);
MVP		0.85
MPC		0.47
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.44
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-45485743;