rs386834161

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_030943.4(AMN):c.1006+34_1007-31delCCTCGCCCCGCCGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000615 in 1,512,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

AMN
NM_030943.4 intron

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 0.688

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 14-102930107-CCGCCCCGCCGCGCCT-C is Pathogenic according to our data. Variant chr14-102930107-CCGCCCCGCCGCGCCT-C is described in ClinVar as [Pathogenic]. Clinvar id is 56742.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102930107-CCGCCCCGCCGCGCCT-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4 link	c.1006+34_1007-31delCCTCGCCCCGCCGCG	intron_variant	Intron 9 of 11	ENST00000299155.10	NP_112205.2	Q9BXJ7-1
AMN	NM_001425246.1 link	c.844+34_845-31delCCTCGCCCCGCCGCG	intron_variant	Intron 9 of 11		NP_001412175.1
AMN	XM_011537203.4 link	c.844+34_845-31delCCTCGCCCCGCCGCG	intron_variant	Intron 9 of 11		XP_011535505.1	B3KP64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10 link	c.1006+34_1007-31delCCTCGCCCCGCCGCG		intron_variant	Intron 9 of 11	1	NM_030943.4	ENSP00000299155.6		Q9BXJ7-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000560

AC:

AN:

107218

Hom.:

AF XY:

0.0000337

AC XY:

AN XY:

59396

show subpopulations

Gnomad AFR exome

AF:

0.000343

Gnomad AMR exome

AF:

0.000151

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000507

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000544

AC:

AN:

1360814

Hom.:

AF XY:

0.0000462

AC XY:

AN XY:

670812

show subpopulations

Gnomad4 AFR exome

AF:

0.0000352

Gnomad4 AMR exome

AF:

0.000128

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000241

Gnomad4 NFE exome

AF:

0.0000572

Gnomad4 OTH exome

AF:

0.000124

GnomAD4 genome

AF:

0.000125

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000793

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Imerslund-Grasbeck syndrome

Pathogenic:2

Jul 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change falls in intron 9 of the AMN gene. It does not directly change the encoded amino acid sequence of the AMN protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs386834161, gnomAD 0.02%). This variant has been observed in individuals with Imerslund-Gr√§sbeck syndrome (PMID: 22929189, 30691194). This variant is also known as c.1006+34_48del15bp. ClinVar contains an entry for this variant (Variation ID: 56742). Studies have shown that this variant results in skipping of exon 9 and introduces a premature termination codon (PMID: 22929189). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. -

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over