Variant 6-110890330-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001634.6(AMD1):c.401T>C(p.Ile134Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000307 in 1,598,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

AMD1
NM_001634.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.53

Variant links:

Genes affected

AMD1 (HGNC:457): (adenosylmethionine decarboxylase 1) This gene encodes an important intermediate enzyme in polyamine biosynthesis. The polyamines spermine, spermidine, and putrescine are low-molecular-weight aliphatic amines essential for cellular proliferation and tumor promotion. Multiple alternatively spliced transcript variants have been identified. Pseudogenes of this gene are found on chromosomes 5, 6, 10, X and Y. [provided by RefSeq, Dec 2013]

AMD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.40296692).

BS2

High AC in GnomAd at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMD1	NM_001634.6 linkuse as main transcript	c.401T>C	p.Ile134Thr	missense_variant	4/9	ENST00000368885.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMD1	ENST00000368885.8 linkuse as main transcript	c.401T>C	p.Ile134Thr	missense_variant	4/9	1	NM_001634.6	P1	P17707-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000126

AC:

AN:

238912

Hom.:

AF XY:

0.00000774

AC XY:

AN XY:

129274

show subpopulations

Gnomad AFR exome

AF:

0.0000633

Gnomad AMR exome

AF:

0.0000324

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1446420

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

719150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000172

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:

0.00000271

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.000191

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000416

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2023

The c.401T>C (p.I134T) alteration is located in exon 4 (coding exon 4) of the AMD1 gene. This alteration results from a T to C substitution at nucleotide position 401, causing the isoleucine (I) at amino acid position 134 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.15

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.79

D;.;.

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;.;D

M_CAP

Benign

0.0043

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.1

L;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.4

N;.;N

REVEL

Benign

0.20

Sift

Benign

0.052

T;.;T

Sift4G

Uncertain

0.040

D;T;T

Polyphen

0.052

B;.;.

Vest4

0.64

MutPred

0.80

Gain of disorder (P = 0.0216);.;.;

MVP

0.20

MPC

1.1

ClinPred

0.24

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over