Genetic Variant NM_015365.3: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: Labcorp Genetics (formerly Invitae), Illumina
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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015365.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMMECR1	NM_015365.3	MANE Select	c.*3C>T	3_prime_UTR	Exon 6 of 6	NP_056180.1	Q9Y4X0-1
AMMECR1	NM_001025580.2		c.*3C>T	3_prime_UTR	Exon 5 of 5	NP_001020751.1	Q9Y4X0-3
AMMECR1	NM_001171689.2		c.*3C>T	3_prime_UTR	Exon 8 of 8	NP_001165160.1	Q9Y4X0-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMMECR1	ENST00000262844.10	TSL:1 MANE Select	c.*3C>T	3_prime_UTR	Exon 6 of 6	ENSP00000262844.5	Q9Y4X0-1
AMMECR1	ENST00000372059.6	TSL:1	c.*3C>T	3_prime_UTR	Exon 5 of 5	ENSP00000361129.2	Q9Y4X0-3
AMMECR1	ENST00000686065.1		c.*119C>T	3_prime_UTR	Exon 7 of 7	ENSP00000509935.1	A0A8I5KSJ4

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over