Variant 7-88114591-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001324418.2(ADAM22):c.481T>C(p.Phe161Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADAM22
NM_001324418.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.45

Variant links:

Genes affected

ADAM22 (HGNC:201): (ADAM metallopeptidase domain 22) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. Unlike other members of the ADAM protein family, the protein encoded by this gene lacks metalloprotease activity since it has no zinc-binding motif. This gene is highly expressed in the brain and may function as an integrin ligand in the brain. In mice, it has been shown to be essential for correct myelination in the peripheral nervous system. Alternative splicing results in several transcript variants.[provided by RefSeq, Dec 2010]

ADAM22 links:

ADAM22 (HGNC:):

ADAM22 links:

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ACMG classification

Classification made for transcript

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
ADAM22	NM_001324418.2 linkuse as main transcript	c.481T>C	p.Phe161Leu	missense_variant	6/32	ENST00000413139.2	NP_001311347.1	H7C3I4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM22	ENST00000413139.2 linkuse as main transcript	c.481T>C	p.Phe161Leu	missense_variant	6/32	5	NM_001324418.2	ENSP00000412085.2		H7C3I4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727134

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jan 07, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

.;T;T;.;T;.;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;T;D;D;D;D;D

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.67

D;D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.;L;L;L;.

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-5.4

D;D;D;D;D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.013

D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

1.0

D;D;.;.;D;D;.

Vest4

0.83

MutPred

0.49

Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);.;Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);.;

MVP

0.53

MPC

1.5

ClinPred

1.0

GERP RS

5.0

Varity_R

0.83

gMVP

0.66

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over