4-48857260-T-C

Position:

• chr4-48857260-T-C

Variant summary

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

The NM_017830.4(OCIAD1):​c.595T>C​(p.Tyr199His) variant causes a missense change. The variant allele was found at a frequency of 0.00000489 in 1,431,442 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: OCIAD1 NM_017830.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00

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 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
OCIAD1	NM_017830.4	c.595T>C	p.Tyr199His	missense_variant	8/9	ENST00000264312.12	NP_060300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCIAD1	ENST00000264312.12	c.595T>C	p.Tyr199His	missense_variant	8/9	1	NM_017830.4	ENSP00000264312.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000489 AC: 7 AN: 1431442 Hom.: 0 Cov.: 27 AF XY: 0.00000562 AC XY: 4 AN XY: 711938

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: 0.00000546

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Dec 20, 2023

The c.610T>C (p.Y204H) alteration is located in exon 8 (coding exon 8) of the OCIAD1 gene. This alteration results from a T to C substitution at nucleotide position 610, causing the tyrosine (Y) at amino acid position 204 to be replaced by a histidine (H). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T;T;T;T;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;.;.;D;.;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D
MetaSVM	Uncertain	0.049	D
MutationAssessor	Benign	1.8	.;L;L;.;L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.0	D;D;D;D;D;D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	D;D;D;.;D;D
Vest4		0.86
MutPred		0.35		.;Gain of glycosylation at Y199 (P = 0.0183);Gain of glycosylation at Y199 (P = 0.0183);.;Gain of glycosylation at Y199 (P = 0.0183);Gain of glycosylation at Y199 (P = 0.0183);
MVP		0.86
MPC		0.56
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs761791560; hg19: chr4-48859277;