dbSNP rs3730836: ZSWIM9:c.-10+392A>T (chr19-48171106-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_199341.4(ZSWIM9):c.-10+392A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 364,280 control chromosomes in the GnomAD database, including 44 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 0.011 ( 31 hom., cov: 32)

Exomes 𝑓: 0.010 ( 13 hom. )

Consequence

ZSWIM9
NM_199341.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0700

Publications

2 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=-0.79).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0108 (1642/152272) while in subpopulation SAS AF = 0.0261 (126/4820). AF 95% confidence interval is 0.0224. There are 31 homozygotes in GnomAd4. There are 797 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM9	NM_199341.4 link	c.-10+392A>T		intron_variant	Intron 1 of 3	ENST00000614654.2	NP_955373.3	Q86XI8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM9	ENST00000614654.2 link	c.-10+392A>T		intron_variant	Intron 1 of 3	5	NM_199341.4	ENSP00000480314.1		Q86XI8-2
ZSWIM9	ENST00000328759.11 link	c.-10+392A>T		intron_variant	Intron 1 of 4	1		ENSP00000331363.7		Q86XI8-1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1640

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00509

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.00443

Gnomad SAS

AF:

0.0257

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0139

GnomAD4 exome

AF:

0.0105

AC:

2224

AN:

212008

Hom.:

AF XY:

0.0100

AC XY:

1007

AN XY:

100218

show subpopulations

African (AFR)

AF:

0.00549

AC:

AN:

4008

American (AMR)

AF:

0.0164

AC:

AN:

244

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

1276

East Asian (EAS)

AF:

0.00347

AC:

AN:

864

South Asian (SAS)

AF:

0.0299

AC:

117

AN:

3912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.0543

AC:

AN:

442

European-Non Finnish (NFE)

AF:

0.0101

AC:

1957

AN:

194092

Other (OTH)

AF:

0.0115

AC:

AN:

7110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

111

221

332

442

553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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:

0.0108

AC:

1642

AN:

152272

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

797

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00510

AC:

212

AN:

41562

American (AMR)

AF:

0.0136

AC:

208

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0185

AC:

AN:

3468

East Asian (EAS)

AF:

0.00444

AC:

AN:

5178

South Asian (SAS)

AF:

0.0261

AC:

126

AN:

4820

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

820

AN:

68006

Other (OTH)

AF:

0.0137

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

166

250

333

416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00889

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.2

(source)

DANN

Benign

0.74

PhyloP100

0.070

PromoterAI

0.032

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over