Genetic Variant ZSWIM7:c.76+170A>C (chr17-15999349-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001042697.2(ZSWIM7):c.76+170A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00373 in 930,604 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 7 hom. )

Consequence

ZSWIM7
NM_001042697.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.147

Publications

0 publications found

Variant links:

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]

ZSWIM7 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: STRONG Submitted by: King Faisal Specialist Hospital and Research Center
ovarian dysgenesis 10
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
colorectal adenoma
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ZSWIM7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 17-15999349-T-G is Benign according to our data. Variant chr17-15999349-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1208591.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042697.2. 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
	ZSWIM7	NM_001042697.2	MANE Select	c.76+170A>C		intron	N/A	NP_001036162.1	Q19AV6
	ZSWIM7	NM_001042698.2		c.76+170A>C		intron	N/A	NP_001036163.1	Q19AV6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZSWIM7	ENST00000399277.6	TSL:1 MANE Select	c.76+170A>C	intron	N/A	ENSP00000382218.1	Q19AV6
ZSWIM7	ENST00000472495.5	TSL:1	c.76+170A>C	intron	N/A	ENSP00000419138.1	Q19AV6
ZSWIM7	ENST00000486706.6	TSL:1	n.89+157A>C	intron	N/A	ENSP00000463327.1	J3QS31

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

415

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00508

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00250

AC:

259

AN:

103756

AF XY:

0.00247

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.000737

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000256

Gnomad NFE exome

AF:

0.00561

Gnomad OTH exome

AF:

0.00123

GnomAD4 exome

AF:

0.00392

AC:

3054

AN:

778258

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

1558

AN XY:

401336

show subpopulations

African (AFR)

AF:

0.000832

AC:

AN:

19242

American (AMR)

AF:

0.000551

AC:

AN:

29058

Ashkenazi Jewish (ASJ)

AF:

0.0000524

AC:

AN:

19080

East Asian (EAS)

AF:

0.00

AC:

AN:

32688

South Asian (SAS)

AF:

0.000797

AC:

AN:

62768

European-Finnish (FIN)

AF:

0.000843

AC:

AN:

32028

Middle Eastern (MID)

AF:

0.00108

AC:

AN:

2772

European-Non Finnish (NFE)

AF:

0.00521

AC:

2833

AN:

543488

Other (OTH)

AF:

0.00291

AC:

108

AN:

37134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

167

333

500

666

833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.00272

AC:

415

AN:

152346

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

189

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41594

American (AMR)

AF:

0.000719

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00509

AC:

346

AN:

68040

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00363

Hom.:

Bravo

AF:

0.00290

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.5

(source)

DANN

Benign

0.55

PhyloP100

0.15

PromoterAI

-0.056

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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