rs141455061

Variant names:

• chr14-102928825-G-A
• rs141455061
• NM_030943.4:c.363G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_030943.4(AMN):​c.363G>A​(p.Gly121Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 1,607,086 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G121G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0059 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (57 hom.)
• Consequence: AMN NM_030943.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.823
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 14-102928825-G-A is Benign according to our data. Variant chr14-102928825-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 532207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.823 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00588 (895/152340) while in subpopulation NFE AF = 0.00578 (393/68038). AF 95% confidence interval is 0.0053. There are 7 homozygotes in GnomAd4. There are 542 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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.363G>A	p.Gly121Gly	synonymous	Exon 5 of 12	NP_112205.2	Q9BXJ7-1
	AMN	NM_001425246.1		c.201G>A	p.Gly67Gly	synonymous	Exon 5 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.363G>A	p.Gly121Gly	synonymous	Exon 5 of 12	ENSP00000299155.6	Q9BXJ7-1
	AMN	ENST00000872999.1		c.306G>A	p.Gly102Gly	synonymous	Exon 5 of 12	ENSP00000543058.1
	AMN	ENST00000559525.1	TSL:3	c.15G>A	p.Gly5Gly	synonymous	Exon 1 of 3	ENSP00000453786.1	H0YMX8

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 895 AN: 152222 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00578

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00595 AC: 1451 AN: 243764 AF XY: 0.00575

Gnomad AFR exome AF: 0.00100

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.000802

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0369

Gnomad NFE exome AF: 0.00619

Gnomad OTH exome AF: 0.00398

GnomAD4 exome AF: 0.00542 AC: 7887 AN: 1454746 Hom.: 57 Cov.: 33 AF XY: 0.00523 AC XY: 3789 AN XY: 723984

African (AFR) AF: 0.000478 AC: 16 AN: 33470

American (AMR) AF: 0.000917 AC: 41 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.000460 AC: 12 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000893 AC: 77 AN: 86252

European-Finnish (FIN) AF: 0.0370 AC: 1726 AN: 46612

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.00518 AC: 5755 AN: 1111808

Other (OTH) AF: 0.00421 AC: 254 AN: 60326

GnomAD4 genome AF: 0.00588 AC: 895 AN: 152340 Hom.: 7 Cov.: 33 AF XY: 0.00728 AC XY: 542 AN XY: 74488

African (AFR) AF: 0.000505 AC: 21 AN: 41576

American (AMR) AF: 0.00229 AC: 35 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.0407 AC: 432 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00578 AC: 393 AN: 68038

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00483 Hom.: 0

Bravo AF: 0.00291

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00442

EpiControl AF: 0.00480

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Imerslund-Grasbeck syndrome (1)
-	-	1	Imerslund-Grasbeck syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.96
PhyloP100		-0.82
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs141455061; hg19: chr14-103395162; COSMIC: COSV54486019; COSMIC: COSV54486019;