chr14-102922666-G-C

Variant names:

• chr14-102922666-G-C
• rs2295829
• NM_030943.4:c.-23G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030943.4(AMN):​c.-23G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,592,304 control chromosomes in the GnomAD database, including 123,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14519 hom., cov: 32)
  • Exomes 𝑓: 0.38 (109353 hom.)
• Consequence: AMN NM_030943.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.64

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=-0.84).
• BP6: Variant 14-102922666-G-C is Benign according to our data. Variant chr14-102922666-G-C is described in ClinVar as [Benign]. Clinvar id is 1262486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4	c.-23G>C		5_prime_UTR_variant	Exon 1 of 12	ENST00000299155.10	NP_112205.2
AMN	NM_001425246.1	c.-204G>C		5_prime_UTR_variant	Exon 1 of 12		NP_001412175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155	c.-23G>C		5_prime_UTR_variant	Exon 1 of 12	1	NM_030943.4	ENSP00000299155.6

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64384 AN: 151722 Hom.: 14493 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.343 AC: 74710 AN: 217602 AF XY: 0.342

Gnomad AFR exome AF: 0.555

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.375

Gnomad EAS exome AF: 0.0940

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.383

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.384 AC: 553364 AN: 1440464 Hom.: 109353 Cov.: 37 AF XY: 0.381 AC XY: 272199 AN XY: 714976

Gnomad4 AFR exome AF: 0.569 AC: 18942 AN: 33306

Gnomad4 AMR exome AF: 0.320 AC: 13419 AN: 41998

Gnomad4 ASJ exome AF: 0.375 AC: 9634 AN: 25682

Gnomad4 EAS exome AF: 0.111 AC: 4355 AN: 39224

Gnomad4 SAS exome AF: 0.296 AC: 24628 AN: 83304

Gnomad4 FIN exome AF: 0.356 AC: 16891 AN: 47426

Gnomad4 NFE exome AF: 0.399 AC: 440476 AN: 1104402

Gnomad4 Remaining exome AF: 0.384 AC: 22907 AN: 59674

GnomAD4 genome AF: 0.425 AC: 64469 AN: 151840 Hom.: 14519 Cov.: 32 AF XY: 0.419 AC XY: 31068 AN XY: 74216

Gnomad4 AFR AF: 0.564 AC: 0.564409 AN: 0.564409

Gnomad4 AMR AF: 0.382 AC: 0.382156 AN: 0.382156

Gnomad4 ASJ AF: 0.369 AC: 0.369013 AN: 0.369013

Gnomad4 EAS AF: 0.107 AC: 0.106935 AN: 0.106935

Gnomad4 SAS AF: 0.280 AC: 0.279601 AN: 0.279601

Gnomad4 FIN AF: 0.349 AC: 0.34893 AN: 0.34893

Gnomad4 NFE AF: 0.399 AC: 0.398774 AN: 0.398774

Gnomad4 OTH AF: 0.397 AC: 0.397156 AN: 0.397156

Alfa AF: 0.296 Hom.: 993

Bravo AF: 0.434

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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: rs2295829; hg19: chr14-103389003; COSMIC: COSV54486859; COSMIC: COSV54486859;