14-102929087-G-C

Variant names:

• chr14-102929087-G-C
• rs144077391
• NM_030943.4:c.514-34G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030943.4(AMN):​c.514-34G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,597,548 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00084 (7 hom.)
• Consequence: AMN NM_030943.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.552

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-102929087-G-C is Benign according to our data. Variant chr14-102929087-G-C is described in ClinVar as [Benign]. Clinvar id is 1657935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00437 (666/152302) while in subpopulation AFR AF = 0.014 (582/41568). AF 95% confidence interval is 0.0131. There are 4 homozygotes in GnomAd4. There are 309 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4	c.514-34G>C		intron_variant	Intron 5 of 11	ENST00000299155.10	NP_112205.2
AMN	NM_001425246.1	c.352-34G>C		intron_variant	Intron 5 of 11		NP_001412175.1
AMN	XM_011537203.4	c.352-34G>C		intron_variant	Intron 5 of 11		XP_011535505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10	c.514-34G>C		intron_variant	Intron 5 of 11	1	NM_030943.4	ENSP00000299155.6

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 665 AN: 152184 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00150 AC: 333 AN: 222038 AF XY: 0.00116

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.000837

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000438

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.000845 AC: 1221 AN: 1445246 Hom.: 7 Cov.: 33 AF XY: 0.000788 AC XY: 567 AN XY: 719354

Gnomad4 AFR exome AF: 0.0163 AC: 544 AN: 33450

Gnomad4 AMR exome AF: 0.00208 AC: 93 AN: 44682

Gnomad4 ASJ exome AF: 0.000498 AC: 13 AN: 26094

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39684

Gnomad4 SAS exome AF: 0.0000116 AC: 1 AN: 86188

Gnomad4 FIN exome AF: 0.000106 AC: 4 AN: 37612

Gnomad4 NFE exome AF: 0.000402 AC: 447 AN: 1111578

Gnomad4 Remaining exome AF: 0.00178 AC: 107 AN: 60196

GnomAD4 genome AF: 0.00437 AC: 666 AN: 152302 Hom.: 4 Cov.: 33 AF XY: 0.00415 AC XY: 309 AN XY: 74470

Gnomad4 AFR AF: 0.0140 AC: 0.0140012 AN: 0.0140012

Gnomad4 AMR AF: 0.00307 AC: 0.00307069 AN: 0.00307069

Gnomad4 ASJ AF: 0.000288 AC: 0.000288018 AN: 0.000288018

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.0000942 AC: 0.000094162 AN: 0.000094162

Gnomad4 NFE AF: 0.000368 AC: 0.00036755 AN: 0.00036755

Gnomad4 OTH AF: 0.00425 AC: 0.00425331 AN: 0.00425331

Alfa AF: 0.000297 Hom.: 0

Bravo AF: 0.00525

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Imerslund-Grasbeck syndrome type 2 Benign:1

Oct 20, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Imerslund-Grasbeck syndrome Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.58
Mutation Taster		=52/34	polymorphism

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

Publications

LitVar

Other links and lift over

dbSNP: rs144077391; hg19: chr14-103395424;