dbSNP rs386834160: AMN:c.1006+16_1006+30delCCATCCCGCCCCGCC (chr14-102930095-GCCCGCCCCATCCCGC-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_030943.4(AMN):c.1006+16_1006+30delCCATCCCGCCCCGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,510 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

AMN
NM_030943.4 intron

Scores

Not classified

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.499

Publications

0 publications found

Variant links:

Genes affected

AMN (HGNC:14604): (amnion associated transmembrane protein) The protein encoded by this gene is a type I transmembrane protein. It is thought to modulate bone morphogenetic protein (BMP) receptor function by serving as an accessory or coreceptor, and thus facilitates or hinders BMP binding. It is known that the mouse AMN gene is expressed in the extraembryonic visceral endoderm layer during gastrulation, but it is found to be mutated in amnionless mouse. The encoded protein has sequence similarity to short gastrulation (Sog) and procollagen IIA proteins in Drosophila. [provided by RefSeq, Jul 2008]

AMN Gene-Disease associations (from GenCC):

Imerslund-Grasbeck syndrome type 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Imerslund-Grasbeck syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AMN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP5

Variant 14-102930095-GCCCGCCCCATCCCGC-G is Pathogenic according to our data. Variant chr14-102930095-GCCCGCCCCATCCCGC-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 56741.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AMN	NM_030943.4 link	c.1006+16_1006+30delCCATCCCGCCCCGCC	intron_variant	Intron 9 of 11	ENST00000299155.10	NP_112205.2
AMN	NM_001425246.1 link	c.844+16_844+30delCCATCCCGCCCCGCC	intron_variant	Intron 9 of 11		NP_001412175.1
AMN	XM_011537203.4 link	c.844+16_844+30delCCATCCCGCCCCGCC	intron_variant	Intron 9 of 11		XP_011535505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10 link	c.1006+10_1006+24delCCCGCCCCATCCCGC		intron_variant	Intron 9 of 11	1	NM_030943.4	ENSP00000299155.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.26e-7

AC:

AN:

1377510

Hom.:

AF XY:

0.00000147

AC XY:

AN XY:

679200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30184

American (AMR)

AF:

0.00

AC:

AN:

34726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24592

East Asian (EAS)

AF:

0.00

AC:

AN:

34740

South Asian (SAS)

AF:

0.0000129

AC:

AN:

77660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4030

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1073458

Other (OTH)

AF:

0.00

AC:

AN:

57208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Imerslund-Grasbeck syndrome

Pathogenic:1

Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.50

Mutation Taster

=99/1

disease causing (ClinVar)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over