4-70202327-A-T

Variant names:

• chr4-70202327-A-T
• rs765404497
• NM_017855.4:c.646A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017855.4(ODAM):​c.646A>T​(p.Met216Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000961 in 1,457,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: ODAM NM_017855.4 missense, splice_region
• Scores: Splicing: ADA: 0.008325
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

Genes affected

ODAM (HGNC:26043): (odontogenic, ameloblast associated) Involved in several processes, including positive regulation of GTPase activity; positive regulation of epithelial cell proliferation involved in wound healing; and positive regulation of macromolecule metabolic process. Located in several cellular components, including extracellular space; mitotic spindle; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.081513226).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017855.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAM	NM_017855.4	MANE Select	c.646A>T	p.Met216Leu	missense splice_region	Exon 9 of 12	NP_060325.3
	ODAM	NM_001385579.1		c.598A>T	p.Met200Leu	missense splice_region	Exon 8 of 11	NP_001372508.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAM	ENST00000683306.1	MANE Select	c.646A>T	p.Met216Leu	missense splice_region	Exon 9 of 12	ENSP00000507531.1	A1E959
	ODAM	ENST00000396094.6	TSL:5	c.646A>T	p.Met216Leu	missense splice_region	Exon 8 of 11	ENSP00000379401.2	A1E959
	ODAM	ENST00000955828.1		c.646A>T	p.Met216Leu	missense splice_region	Exon 9 of 12	ENSP00000625887.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000400 AC: 10 AN: 250266 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000493

GnomAD4 exome AF: 0.00000961 AC: 14 AN: 1457484 Hom.: 0 Cov.: 29 AF XY: 0.00000827 AC XY: 6 AN XY: 725184

African (AFR) AF: 0.00 AC: 0 AN: 33316

American (AMR) AF: 0.000270 AC: 12 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 86154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108584

Other (OTH) AF: 0.0000166 AC: 1 AN: 60184

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000577 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.59
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.014
Sift	Benign	0.12	T
Sift4G	Benign	0.29	T
Polyphen		0.0040	B
Vest4		0.28
MutPred		0.28		Loss of disorder (P = 0.2275)
MVP		0.040
MPC		0.0075
ClinPred		0.034	T
GERP RS		1.2
Varity_R		0.13
gMVP		0.19
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0083
dbscSNV1_RF	Benign	0.22
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs765404497; hg19: chr4-71068044;