NM_030943.4:c.43+146C>A

Variant names:

• chr14-102922877-C-A
• rs1190225
• NM_030943.4:c.43+146C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030943.4(AMN):​c.43+146C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AMN NM_030943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4	c.43+146C>A		intron_variant	Intron 1 of 11	ENST00000299155.10	NP_112205.2
AMN	NM_001425246.1	c.-120+127C>A		intron_variant	Intron 1 of 11		NP_001412175.1
AMN	XM_011537203.4	c.-741C>A		upstream_gene_variant			XP_011535505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10	c.43+146C>A		intron_variant	Intron 1 of 11	1	NM_030943.4	ENSP00000299155.6
AMN	ENST00000541086.5	n.-45C>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 998238 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 494744

African (AFR) AF: 0.00 AC: 0 AN: 23112

American (AMR) AF: 0.00 AC: 0 AN: 28224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18746

East Asian (EAS) AF: 0.00 AC: 0 AN: 31896

South Asian (SAS) AF: 0.00 AC: 0 AN: 61066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3082

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 757164

Other (OTH) AF: 0.00 AC: 0 AN: 44142

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.61
DANN	Benign	0.24
PhyloP100		-1.4
PromoterAI		-0.31	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1190225; hg19: chr14-103389214;