14-102929439-G-T

Variant names:

• chr14-102929439-G-T
• NM_030943.4:c.663G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030943.4(AMN):​c.663G>T​(p.Trp221Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,378,776 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: AMN NM_030943.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4	c.663G>T	p.Trp221Cys	missense_variant	Exon 7 of 12	ENST00000299155.10	NP_112205.2
AMN	NM_001425246.1	c.501G>T	p.Trp167Cys	missense_variant	Exon 7 of 12		NP_001412175.1
AMN	XM_011537203.4	c.501G>T	p.Trp167Cys	missense_variant	Exon 7 of 12		XP_011535505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10	c.663G>T	p.Trp221Cys	missense_variant	Exon 7 of 12	1	NM_030943.4	ENSP00000299155.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1378776 Hom.: 0 Cov.: 33 AF XY: 0.00000147 AC XY: 1 AN XY: 680298

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.28e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	0.16
Eigen_PC	Benign	0.0091
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Uncertain	2.0	M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.51		Gain of catalytic residue at Q219 (P = 0);
MVP		0.94
MPC		1.8
ClinPred		0.96	D
GERP RS		3.3
Varity_R		0.43
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-103395776;