Genetic Variant DEFA3:p.Ala38Ala (chr8-7016737-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_005217.4(DEFA3):c.114G>A(p.Ala38Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000078 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DEFA3
NM_005217.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.67

Publications

0 publications found

Variant links:

Genes affected

DEFA3 (HGNC:2762): (defensin alpha 3) Defensins are a family of antimicrobial and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. The protein encoded by this gene, defensin, alpha 3, is found in the microbicidal granules of neutrophils and likely plays a role in phagocyte-mediated host defense. Several alpha defensin genes are clustered on chromosome 8. This gene differs from defensin, alpha 1 by only one amino acid. This gene and the gene encoding defensin, alpha 1 are both subject to copy number variation. [provided by RefSeq, Oct 2014]

DEFA3 links:

LOC124901875 (HGNC:):

LOC124901875 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-7016737-C-T is Benign according to our data. Variant chr8-7016737-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2658353.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.67 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005217.4. 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
	DEFA3	NM_005217.4	MANE Select	c.114G>A	p.Ala38Ala	synonymous	Exon 2 of 3	NP_005208.1	Q6EZE9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DEFA3	ENST00000327857.7	TSL:1 MANE Select	c.114G>A	p.Ala38Ala	synonymous	Exon 2 of 3	ENSP00000328359.2	P59666
DEFA3	ENST00000867396.1		c.114G>A	p.Ala38Ala	synonymous	Exon 1 of 2	ENSP00000537455.1
DEFA3	ENST00000960561.1		c.114G>A	p.Ala38Ala	synonymous	Exon 3 of 4	ENSP00000630620.1

Frequencies

GnomAD3 genomes

AF:

0.0000820

AC:

AN:

146280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000762

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000690

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000878

Gnomad FIN

AF:

0.000195

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000303

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000181

AC:

AN:

71768

AF XY:

0.000108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000506

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000120

Gnomad NFE exome

AF:

0.0000689

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000784

AC:

101

AN:

1288046

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

639322

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

27902

American (AMR)

AF:

0.000421

AC:

AN:

33270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22304

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38726

South Asian (SAS)

AF:

0.000590

AC:

AN:

72866

European-Finnish (FIN)

AF:

0.000120

AC:

AN:

50190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3630

European-Non Finnish (NFE)

AF:

0.0000284

AC:

AN:

985314

Other (OTH)

AF:

0.000167

AC:

AN:

53844

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.318

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000888

AC:

AN:

146392

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

71380

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000101

AC:

AN:

39506

American (AMR)

AF:

0.0000689

AC:

AN:

14512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3378

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.000879

AC:

AN:

4552

European-Finnish (FIN)

AF:

0.000195

AC:

AN:

10256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000303

AC:

AN:

65916

Other (OTH)

AF:

0.00

AC:

AN:

1976

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000521358), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.346

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:

0.00

Hom.:

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

-0.90

CADD

Benign

3.2

(source)

DANN

Benign

0.35

PhyloP100

-1.7

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

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