14-102922877-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030943.4(AMN):c.43+146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 1,149,760 control chromosomes in the GnomAD database, including 3,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (314 hom., cov: 33)
  • Exomes 𝑓: 0.072 (2952 hom.)
• Consequence: AMN NM_030943.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-102922877-C-T is Benign according to our data. Variant chr14-102922877-C-T is described in ClinVar as [Benign]. Clinvar id is 1268789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMN	NM_030943.4	c.43+146C>T		intron_variant		ENST00000299155.10
AMN	XM_011537202.4	c.-120+127C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMN	ENST00000299155.10	c.43+146C>T		intron_variant		1	NM_030943.4	P1
AMN	ENST00000541086.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8795 AN: 152170 Hom.: 314 Cov.: 33

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0429

Gnomad FIN AF: 0.0617

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.0516

GnomAD4 exome AF: 0.0724 AC: 72221 AN: 997472 Hom.: 2952 Cov.: 13 AF XY: 0.0710 AC XY: 35104 AN XY: 494376

Gnomad4 AFR exome AF: 0.0257

Gnomad4 AMR exome AF: 0.0309

Gnomad4 ASJ exome AF: 0.0660

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.0440

Gnomad4 FIN exome AF: 0.0702

Gnomad4 NFE exome AF: 0.0748

Gnomad4 OTH exome AF: 0.0656

GnomAD4 genome AF: 0.0578 AC: 8798 AN: 152288 Hom.: 314 Cov.: 33 AF XY: 0.0590 AC XY: 4397 AN XY: 74472

Gnomad4 AFR AF: 0.0304

Gnomad4 AMR AF: 0.0434

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0431

Gnomad4 FIN AF: 0.0617

Gnomad4 NFE AF: 0.0731

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.0639 Hom.: 53

Bravo AF: 0.0565

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.80
Dann	Benign	0.43

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: rs1190225; hg19: chr14-103389214; COSMIC: COSV54488105; COSMIC: COSV54488105;