rs386834163

Variant names:

• chr14-102930171-CCCTCGGCG-C
• rs386834163
• NM_030943.4:c.1014_1021delCCTCGGCG

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_030943.4(AMN):​c.1014_1021delCCTCGGCG​(p.Leu339ProfsTer167) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000749 in 1,335,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: AMN NM_030943.4 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.94

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-102930171-CCCTCGGCG-C is Pathogenic according to our data. Variant chr14-102930171-CCCTCGGCG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 56744.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-102930171-CCCTCGGCG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4	c.1014_1021delCCTCGGCG	p.Leu339ProfsTer167	frameshift_variant	Exon 10 of 12	ENST00000299155.10	NP_112205.2
AMN	NM_001425246.1	c.852_859delCCTCGGCG	p.Leu285ProfsTer167	frameshift_variant	Exon 10 of 12		NP_001412175.1
AMN	XM_011537203.4	c.852_859delCCTCGGCG	p.Leu285ProfsTer167	frameshift_variant	Exon 10 of 12		XP_011535505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10	c.1014_1021delCCTCGGCG	p.Leu339ProfsTer167	frameshift_variant	Exon 10 of 12	1	NM_030943.4	ENSP00000299155.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1335512 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 659262

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000339

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Imerslund-Grasbeck syndrome Pathogenic:1

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

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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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: rs386834163; hg19: chr14-103396508;