rs559485648

Variant names:

• chr8-7016737-C-G
• rs559485648
• NM_005217.4:c.114G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-7016737-C-G
• chr8-7016737-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005217.4(DEFA3):​c.114G>C​(p.Ala38Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A38A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 26)
• Consequence: DEFA3 NM_005217.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 0 publications found

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]

LOC124901875 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• 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>C	p.Ala38Ala	synonymous	Exon 2 of 3	NP_005208.1	Q6EZE9

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.45
DANN	Benign	0.42
PhyloP100		-1.7

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

Other links and lift over

dbSNP: rs559485648; hg19: chr8-6874259;