rs764090698

Variant names:

• chr16-89954370-C-A
• NM_001242818.2:c.118C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89954370-C-A
• chr16-89954370-C-G
• chr16-89954370-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001242818.2(DEF8):​c.118C>A​(p.Pro40Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P40S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DEF8 NM_001242818.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04667422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEF8	NM_001242818.2	c.118C>A	p.Pro40Thr	missense_variant	Exon 3 of 13	ENST00000563594.6	NP_001229747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEF8	ENST00000563594.6	c.118C>A	p.Pro40Thr	missense_variant	Exon 3 of 13	1	NM_001242818.2	ENSP00000458019.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461122 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726868

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.086
DANN	Benign	0.91
DEOGEN2	Benign	0.010	.;T;.;.;T;.;T;.;T;.;T;T;.;.;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.70	.;T;T;T;T;T;T;T;T;.;T;T;.;T;T;T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.047	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;.;.;.;.;.;.;.;N;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.010	N;N;.;.;N;N;N;N;N;N;N;N;N;N;N;N;D
REVEL	Benign	0.018
Sift	Benign	0.28	T;T;.;.;T;T;T;D;D;T;T;T;D;T;T;T;T
Sift4G	Benign	0.089	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0060	B;.;B;B;.;.;.;.;B;B;.;.;B;.;B;.;.
Vest4		0.068
MutPred		0.15		.;.;.;.;.;.;.;.;Gain of phosphorylation at P101 (P = 0.0056);.;.;.;.;.;.;.;.;
MVP		0.014
MPC		0.054
ClinPred		0.086	T
GERP RS		-6.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.077

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-90020778;