Genetic Variant ZSWIM7:p.Thr77Lys (chr17-15981116-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/21 in silico tools predict a benign 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. T77P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

ZSWIM7
NM_001042697.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.652

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.230C>A	p.Thr77Lys	missense	Exon 4 of 5	NP_001036162.1	Q19AV6
	ZSWIM7	NM_001042698.2		c.230C>A	p.Thr77Lys	missense	Exon 4 of 6	NP_001036163.1	Q19AV6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSWIM7	ENST00000399277.6	TSL:1 MANE Select	c.230C>A	p.Thr77Lys	missense	Exon 4 of 5	ENSP00000382218.1	Q19AV6
ZSWIM7	ENST00000472495.5	TSL:1	c.230C>A	p.Thr77Lys	missense	Exon 4 of 6	ENSP00000419138.1	Q19AV6
ZSWIM7	ENST00000486706.6	TSL:1	n.*240C>A		non_coding_transcript_exon	Exon 5 of 6	ENSP00000463327.1	J3QS31

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461466

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727044

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111710

Other (OTH)

AF:

0.0000166

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.26

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.78

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.65

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.28

Sift

Uncertain

0.024

Sift4G

Benign

0.54

Polyphen

0.83

Vest4

0.78

MutPred

0.56

Gain of methylation at T77 (P = 0.0034)

MVP

0.20

MPC

0.58

ClinPred

0.96

GERP RS

0.91

Varity_R

0.28

gMVP

0.69

Mutation Taster

=69/31

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over