4-48885557-A-G

Position:

• chr4-48885557-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001014446.3(OCIAD2):​c.392T>C​(p.Leu131Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,912 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OCIAD2 NM_001014446.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.94

Genes affected

OCIAD2 (HGNC:28685): (OCIA domain containing 2) Predicted to be involved in endocytosis; hematopoietic stem cell homeostasis; and positive regulation of receptor signaling pathway via JAK-STAT. Predicted to act upstream of or within response to bacterium. Predicted to be located in Golgi apparatus; endosome; and lysosome. [provided by Alliance of Genome Resources, Apr 2022]

OCIAD2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCIAD2	NM_001014446.3	c.392T>C	p.Leu131Pro	missense_variant	7/7	ENST00000508632.6	NP_001014446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCIAD2	ENST00000508632.6	c.392T>C	p.Leu131Pro	missense_variant	7/7	1	NM_001014446.3	ENSP00000423014.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449912 Hom.: 0 Cov.: 27 AF XY: 0.00000277 AC XY: 2 AN XY: 722180

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.392T>C (p.L131P) alteration is located in exon 7 (coding exon 6) of the OCIAD2 gene. This alteration results from a T to C substitution at nucleotide position 392, causing the leucine (L) at amino acid position 131 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.082
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.20
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.58
MutPred		0.48		Gain of relative solvent accessibility (P = 0.0023);
MVP		0.41
MPC		0.54
ClinPred		0.75	D
GERP RS		5.3
Varity_R		0.15
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr4-48887574;