dbSNP rs180715560: AMMECR1:c.*3C>T (chrX-110198517-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015365.3(AMMECR1):c.*3C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0000363 in 1,158,586 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.000032 ( 0 hom. 7 hem. )

Consequence

AMMECR1
NM_015365.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.88

Publications

0 publications found

Variant links:

Genes affected

AMMECR1 (HGNC:467): (AMMECR nuclear protein 1) The exact function of this gene is not known, however, submicroscopic deletion of the X chromosome including this gene, COL4A5, and FACL4 genes, result in a contiguous gene deletion syndrome, the AMME complex (Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

AMMECR1 Gene-Disease associations (from GenCC):

midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae)
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

AMMECR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AMMECR1	NM_015365.3 link	c.*3C>T	3_prime_UTR_variant	Exon 6 of 6	ENST00000262844.10	NP_056180.1
AMMECR1	NM_001025580.2 link	c.*3C>T	3_prime_UTR_variant	Exon 5 of 5		NP_001020751.1
AMMECR1	NM_001171689.2 link	c.*3C>T	3_prime_UTR_variant	Exon 8 of 8		NP_001165160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMMECR1	ENST00000262844.10 link	c.*3C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_015365.3	ENSP00000262844.5		Q9Y4X0-1

Frequencies

GnomAD3 genomes

AF:

0.0000718

AC:

AN:

111495

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000979

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000754

Gnomad OTH

AF:

0.000667

GnomAD2 exomes

AF:

0.0000267

AC:

AN:

150080

AF XY:

0.0000229

show subpopulations

Gnomad AFR exome

AF:

0.000167

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000295

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000325

AC:

AN:

1047037

Hom.:

Cov.:

AF XY:

0.0000215

AC XY:

AN XY:

326319

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25010

American (AMR)

AF:

0.00

AC:

AN:

32379

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17209

East Asian (EAS)

AF:

0.00

AC:

AN:

29206

South Asian (SAS)

AF:

0.00

AC:

AN:

47971

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39213

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3899

European-Non Finnish (NFE)

AF:

0.0000396

AC:

AN:

808075

Other (OTH)

AF:

0.0000454

AC:

AN:

44075

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000717

AC:

AN:

111549

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33737

show subpopulations

African (AFR)

AF:

0.0000977

AC:

AN:

30701

American (AMR)

AF:

0.00

AC:

AN:

10515

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3524

South Asian (SAS)

AF:

0.00

AC:

AN:

2648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000754

AC:

AN:

53071

Other (OTH)

AF:

0.000659

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism

(source)

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

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rs180715560

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over