16-89957794-G-T

Variant names:

• chr16-89957794-G-T
• rs8049897
• NM_001242818.2:c.372+134G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001242818.2(DEF8):​c.372+134G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 982,334 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: DEF8 NM_001242818.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 0 publications found

Genes affected

DEF8 (HGNC:25969): (differentially expressed in FDCP 8 homolog) Predicted to enable metal ion binding activity. Predicted to be involved in lysosome localization; positive regulation of bone resorption; and positive regulation of ruffle assembly. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242818.2. 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
	DEF8	NM_001242818.2	MANE Select	c.372+134G>T		intron	N/A	NP_001229747.1	Q6ZN54-5
	DEF8	NM_001438955.1		c.555+134G>T		intron	N/A	NP_001425884.1
	DEF8	NM_207514.3		c.555+134G>T		intron	N/A	NP_997397.1	Q6ZN54-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEF8	ENST00000563594.6	TSL:1 MANE Select	c.372+134G>T		intron	N/A	ENSP00000458019.1	Q6ZN54-5
	DEF8	ENST00000610455.4	TSL:1	c.372+134G>T		intron	N/A	ENSP00000480073.1	Q6ZN54-2
	DEF8	ENST00000567999.5	TSL:1	c.372+134G>T		intron	N/A	ENSP00000457072.1	H3BT87

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 982334 Hom.: 0 AF XY: 0.00000206 AC XY: 1 AN XY: 485174

African (AFR) AF: 0.00 AC: 0 AN: 21930

American (AMR) AF: 0.0000555 AC: 1 AN: 18026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16630

East Asian (EAS) AF: 0.00 AC: 0 AN: 32572

South Asian (SAS) AF: 0.00 AC: 0 AN: 55268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2986

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 750828

Other (OTH) AF: 0.00 AC: 0 AN: 43076

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		-0.28

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: rs8049897; hg19: chr16-90024202;