1-186419020-G-A

Position:

• chr1-186419020-G-A

Variant summary

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

The NM_017847.6(ODR4):​c.1309G>A​(p.Ala437Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ODR4 NM_017847.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81

Genes affected

ODR4 (HGNC:24299): (odr-4 GPCR localization factor homolog) Predicted to be involved in protein localization. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.4055453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODR4	NM_017847.6	c.1309G>A	p.Ala437Thr	missense_variant	14/14	ENST00000287859.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODR4	ENST00000287859.11	c.1309G>A	p.Ala437Thr	missense_variant	14/14	1	NM_017847.6	P1
ODR4	ENST00000367470.8	c.1240G>A	p.Ala414Thr	missense_variant	13/13	5
ODR4	ENST00000419367.8	c.1213G>A	p.Ala405Thr	missense_variant	13/13	2
ODR4	ENST00000461662.1	n.290G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455544 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723240

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: 0.00

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 14, 2021

The c.1309G>A (p.A437T) alteration is located in exon 14 (coding exon 13) of the C1orf27 gene. This alteration results from a G to A substitution at nucleotide position 1309, causing the alanine (A) at amino acid position 437 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	.;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.5	.;.;M
MutationTaster	Benign	0.98	D;D;D;D
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		0.99	.;D;D
Vest4		0.56
MutPred		0.38		.;.;Loss of helix (P = 0.0558);
MVP		0.45
MPC		0.56
ClinPred		0.96	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.69

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: chr1-186388152;