rs386834175

chr14-102929454-GCTCCAGCCCCTGGGCGGCCGCTGCCCCCAGGCCGCCTGCCACAGCGCC-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PM4 PP5

The NM_030943.4(AMN):c.683_730del(p.Gln228_Leu243del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000657 in 152,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: AMN NM_030943.4 inframe_deletion
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.84

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a domain VWFC (size 52) in uniprot entity AMNLS_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_030943.4
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_030943.4.
• PP5: Variant 14-102929454-GCTCCAGCCCCTGGGCGGCCGCTGCCCCCAGGCCGCCTGCCACAGCGCC-G is Pathogenic according to our data. Variant chr14-102929454-GCTCCAGCCCCTGGGCGGCCGCTGCCCCCAGGCCGCCTGCCACAGCGCC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 56757.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-102929454-GCTCCAGCCCCTGGGCGGCCGCTGCCCCCAGGCCGCCTGCCACAGCGCC-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMN	NM_030943.4	c.683_730del	p.Gln228_Leu243del	inframe_deletion	7/12	ENST00000299155.10
AMN	XM_011537202.4	c.521_568del	p.Gln174_Leu189del	inframe_deletion	7/12
AMN	XM_011537203.4	c.521_568del	p.Gln174_Leu189del	inframe_deletion	7/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMN	ENST00000299155.10	c.683_730del	p.Gln228_Leu243del	inframe_deletion	7/12	1	NM_030943.4	P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Imerslund-Grasbeck syndrome Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

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

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs386834175; hg19: chr14-103395791;