14-102930107-CCGCCCCGCCGCGCCT-CCGCCCCGCCGCGCCTCGCCCCGCCGCGCCT

Variant names:

• chr14-102930107-C-CCGCCCCGCCGCGCCT
• rs386834161
• NM_030943.4:c.1006+34_1007-31dupCCTCGCCCCGCCGCG

Variant summary

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

The NM_030943.4(AMN):​c.1006+34_1007-31dupCCTCGCCCCGCCGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000588 in 1,360,836 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 INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: AMN NM_030943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4	c.1006+34_1007-31dupCCTCGCCCCGCCGCG		intron_variant	Intron 9 of 11	ENST00000299155.10	NP_112205.2
AMN	NM_001425246.1	c.844+34_845-31dupCCTCGCCCCGCCGCG		intron_variant	Intron 9 of 11		NP_001412175.1
AMN	XM_011537203.4	c.844+34_845-31dupCCTCGCCCCGCCGCG		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	c.1006+34_1007-31dupCCTCGCCCCGCCGCG		intron_variant	Intron 9 of 11	1	NM_030943.4	ENSP00000299155.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000588 AC: 8 AN: 1360836 Hom.: 0 Cov.: 33 AF XY: 0.00000596 AC XY: 4 AN XY: 670818

African (AFR) AF: 0.00 AC: 0 AN: 28440

American (AMR) AF: 0.00 AC: 0 AN: 31322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23532

East Asian (EAS) AF: 0.00 AC: 0 AN: 33622

South Asian (SAS) AF: 0.00 AC: 0 AN: 75154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41496

Middle Eastern (MID) AF: 0.000252 AC: 1 AN: 3974

European-Non Finnish (NFE) AF: 0.00000562 AC: 6 AN: 1066920

Other (OTH) AF: 0.0000177 AC: 1 AN: 56376

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs386834161; hg19: chr14-103396444;