Genetic Variant ALDH1A3:c.99+7C>A (chr15-100880013-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_000693.4(ALDH1A3):c.99+7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000667 in 1,454,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

ALDH1A3
NM_000693.4 splice_region, intron

Scores

Splicing: ADA: 0.0001155

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.13

Publications

0 publications found

Variant links:

Genes affected

ALDH1A3 (HGNC:409): (aldehyde dehydrogenase 1 family member A3) This gene encodes an aldehyde dehydrogenase enzyme that uses retinal as a substrate. Mutations in this gene have been associated with microphthalmia, isolated 8, and expression changes have also been detected in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ALDH1A3 Gene-Disease associations (from GenCC):

isolated anophthalmia-microphthalmia syndrome
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
isolated microphthalmia 8
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ALDH1A3 links:

LOC124903575 (HGNC:):

LOC124903575 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 15-100880013-C-A is Benign according to our data. Variant chr15-100880013-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3037497.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000693.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A3	NM_000693.4	MANE Select	c.99+7C>A		splice_region intron	N/A	NP_000684.2	P47895
	ALDH1A3	NM_001293815.2		c.99+7C>A		splice_region intron	N/A	NP_001280744.1	H0Y2X5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALDH1A3	ENST00000329841.10	TSL:1 MANE Select	c.99+7C>A	splice_region intron	N/A	ENSP00000332256.5	P47895
ALDH1A3	ENST00000346623.6	TSL:1	c.99+7C>A	splice_region intron	N/A	ENSP00000343294.6	H0Y2X5
ALDH1A3	ENST00000560555.1	TSL:1	n.159+7C>A	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151796

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000177

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000505

AC:

AN:

79222

AF XY:

0.0000443

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000148

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000645

AC:

AN:

1302344

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

640726

show subpopulations

African (AFR)

AF:

0.0000377

AC:

AN:

26526

American (AMR)

AF:

0.00

AC:

AN:

25178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22792

East Asian (EAS)

AF:

0.00

AC:

AN:

27556

South Asian (SAS)

AF:

0.00

AC:

AN:

69828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4972

European-Non Finnish (NFE)

AF:

0.0000805

AC:

AN:

1030692

Other (OTH)

AF:

0.00

AC:

AN:

53052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000856

AC:

AN:

151796

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67886

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ALDH1A3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.2

(source)

DANN

Benign

0.91

PhyloP100

-2.1

PromoterAI

-0.00090

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.058

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