dbSNP rs3730837: ZSWIM9:c.-10+385T>C (chr19-48171099-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_199341.4(ZSWIM9):c.-10+385T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 327,416 control chromosomes in the GnomAD database, including 1,383 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 0.069 ( 513 hom., cov: 31)

Exomes 𝑓: 0.096 ( 870 hom. )

Consequence

ZSWIM9
NM_199341.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0330

Publications

3 publications found

Variant links:

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]

ZSWIM9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199341.4. 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
	ZSWIM9	NM_199341.4	MANE Select	c.-10+385T>C		intron	N/A	NP_955373.3	Q86XI8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZSWIM9	ENST00000614654.2	TSL:5 MANE Select	c.-10+385T>C	intron	N/A	ENSP00000480314.1	Q86XI8-2
ZSWIM9	ENST00000328759.11	TSL:1	c.-10+385T>C	intron	N/A	ENSP00000331363.7	Q86XI8-1
ZSWIM9	ENST00000884364.1		c.-306T>C	5_prime_UTR	Exon 1 of 4	ENSP00000554423.1

Frequencies

GnomAD3 genomes

AF:

0.0691

AC:

10510

AN:

152058

Hom.:

513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0693

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0556

Gnomad FIN

AF:

0.0873

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0832

GnomAD4 exome

AF:

0.0955

AC:

16742

AN:

175240

Hom.:

870

AF XY:

0.0966

AC XY:

8024

AN XY:

83030

show subpopulations

African (AFR)

AF:

0.0101

AC:

AN:

3360

American (AMR)

AF:

0.0455

AC:

AN:

198

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

111

AN:

1044

East Asian (EAS)

AF:

0.00

AC:

AN:

706

South Asian (SAS)

AF:

0.0669

AC:

221

AN:

3304

European-Finnish (FIN)

AF:

0.104

AC:

AN:

Middle Eastern (MID)

AF:

0.0879

AC:

AN:

364

European-Non Finnish (NFE)

AF:

0.0985

AC:

15794

AN:

160346

Other (OTH)

AF:

0.0913

AC:

536

AN:

5870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

758

1517

2275

3034

3792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

780

1560

2340

3120

3900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0690

AC:

10506

AN:

152176

Hom.:

513

Cov.:

AF XY:

0.0678

AC XY:

5040

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0176

AC:

731

AN:

41526

American (AMR)

AF:

0.0692

AC:

1058

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

367

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.0559

AC:

269

AN:

4812

European-Finnish (FIN)

AF:

0.0873

AC:

925

AN:

10600

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6958

AN:

67992

Other (OTH)

AF:

0.0823

AC:

174

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

503

1006

1508

2011

2514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0772

Hom.:

415

Bravo

AF:

0.0638

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.6

(source)

DANN

Benign

0.52

PhyloP100

-0.033

PromoterAI

0.0062

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over