NM_030943.4:c.10C>T

Variant names:

• chr14-102922698-C-T
• NM_030943.4:c.10C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_030943.4(AMN):​c.10C>T​(p.Leu4Leu) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AMN NM_030943.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.882
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 14-102922698-C-T is Benign according to our data. Variant chr14-102922698-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3723205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.882 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030943.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMN	NM_030943.4	MANE Select	c.10C>T	p.Leu4Leu	synonymous	Exon 1 of 12	NP_112205.2	Q9BXJ7-1
	AMN	NM_001425246.1		c.-172C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001412175.1	B3KP64
	AMN	NM_001425246.1		c.-172C>T		5_prime_UTR	Exon 1 of 12	NP_001412175.1	B3KP64

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMN	ENST00000299155.10	TSL:1 MANE Select	c.10C>T	p.Leu4Leu	synonymous	Exon 1 of 12	ENSP00000299155.6	Q9BXJ7-1
	AMN	ENST00000872999.1		c.10C>T	p.Leu4Leu	synonymous	Exon 1 of 12	ENSP00000543058.1
	AMN	ENST00000541086.5	TSL:2	n.-224C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.91e-7 AC: 1 AN: 1446688 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 718640

African (AFR) AF: 0.00 AC: 0 AN: 33384

American (AMR) AF: 0.00 AC: 0 AN: 42888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25772

East Asian (EAS) AF: 0.00 AC: 0 AN: 39310

South Asian (SAS) AF: 0.00 AC: 0 AN: 83740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5292

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107616

Other (OTH) AF: 0.00 AC: 0 AN: 59864

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Imerslund-Grasbeck syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.84
PhyloP100		0.88
PromoterAI		-0.015	Neutral

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

hg19: chr14-103389035;