NM_001042697.2:c.230C>A

Variant names:

• chr17-15981116-G-T
• rs535548098
• NM_001042697.2:c.230C>A

Variant summary

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

The NM_001042697.2(ZSWIM7):​c.230C>A​(p.Thr77Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: ZSWIM7 NM_001042697.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.652

Genes affected

ZSWIM7 (HGNC:26993): (zinc finger SWIM-type containing 7) Predicted to enable zinc ion binding activity. Involved in double-strand break repair via homologous recombination and protein stabilization. Part of Shu complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM7	NM_001042697.2	c.230C>A	p.Thr77Lys	missense_variant	Exon 4 of 5	ENST00000399277.6	NP_001036162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM7	ENST00000399277.6	c.230C>A	p.Thr77Lys	missense_variant	Exon 4 of 5	1	NM_001042697.2	ENSP00000382218.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1461466 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 727044

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: 0.0000108

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.26	T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.024	D;D
Sift4G	Benign	0.54	T;T
Polyphen		0.83	P;P
Vest4		0.78
MutPred		0.56		Gain of methylation at T77 (P = 0.0034);Gain of methylation at T77 (P = 0.0034);
MVP		0.20
MPC		0.58
ClinPred		0.96	D
GERP RS		0.91
Varity_R		0.28
gMVP		0.69

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: rs535548098; hg19: chr17-15884430;