chr4-48850012-A-G

Position:

• chr4-48850012-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017830.4(OCIAD1):​c.307A>G​(p.Lys103Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,308 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OCIAD1 NM_017830.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.76

Genes affected

OCIAD1 (HGNC:16074): (OCIA domain containing 1) Predicted to be involved in several processes, including hematopoietic stem cell homeostasis; positive regulation of receptor signaling pathway via JAK-STAT; and regulation of stem cell differentiation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

OCIAD1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3813388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCIAD1	NM_017830.4	c.307A>G	p.Lys103Glu	missense_variant	6/9	ENST00000264312.12	NP_060300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCIAD1	ENST00000264312.12	c.307A>G	p.Lys103Glu	missense_variant	6/9	1	NM_017830.4	ENSP00000264312.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461308 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726910

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Oct 09, 2024

The c.322A>G (p.K108E) alteration is located in exon 6 (coding exon 6) of the OCIAD1 gene. This alteration results from a A to G substitution at nucleotide position 322, causing the lysine (K) at amino acid position 108 to be replaced by a glutamic acid (E). 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	0.28
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	.;T;.;.;T;.;T;T;T;.;T;.;T;.;.;T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;T;T;D;.;D;T;T;.;.;D;D;T;D;D;.;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.38	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.8	.;.;.;.;L;L;.;.;L;L;.;.;.;.;L;L;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.5	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.20	T;D;T;T;D;T;T;T;D;T;T;D;D;T;T;D;D
Sift4G	Uncertain	0.056	T;T;D;T;T;T;D;D;T;T;T;T;T;T;T;T;T
Polyphen		0.98, 0.95, 0.24	.;D;.;.;P;B;.;.;P;.;.;.;.;.;.;P;P
Vest4		0.34, 0.33, 0.32, 0.34, 0.35, 0.33
MutPred		0.51		Loss of methylation at K103 (P = 0.0053);.;.;Loss of methylation at K103 (P = 0.0053);Loss of methylation at K103 (P = 0.0053);Loss of methylation at K103 (P = 0.0053);Loss of methylation at K103 (P = 0.0053);Loss of methylation at K103 (P = 0.0053);Loss of methylation at K103 (P = 0.0053);Loss of methylation at K103 (P = 0.0053);.;.;.;.;Loss of methylation at K103 (P = 0.0053);Loss of methylation at K103 (P = 0.0053);Loss of methylation at K103 (P = 0.0053);
MVP		0.38
MPC		0.25
ClinPred		0.93	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.86

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: chr4-48852029;