12-85286836-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006982.3(ALX1):​c.532-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,561,024 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0033 ( 10 hom. )

Consequence

ALX1
NM_006982.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0790
Variant links:
Genes affected
ALX1 (HGNC:1494): (ALX homeobox 1) The specific function of this gene has yet to be determined in humans; however, in rodents, it is necessary for survival of the forebrain mesenchyme and may also be involved in development of the cervix. Mutations in the mouse gene lead to neural tube defects such as acrania and meroanencephaly. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 12-85286836-T-C is Benign according to our data. Variant chr12-85286836-T-C is described in ClinVar as [Benign]. Clinvar id is 1991732.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ALX1NM_006982.3 linkuse as main transcriptc.532-17T>C intron_variant ENST00000316824.4 NP_008913.2 Q15699V9HWA7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ALX1ENST00000316824.4 linkuse as main transcriptc.532-17T>C intron_variant 1 NM_006982.3 ENSP00000315417.3 Q15699

Frequencies

GnomAD3 genomes
AF:
0.00234
AC:
355
AN:
151880
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000483
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.000592
Gnomad ASJ
AF:
0.00549
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00565
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00360
Gnomad OTH
AF:
0.000960
GnomAD3 exomes
AF:
0.00304
AC:
586
AN:
192896
Hom.:
2
AF XY:
0.00293
AC XY:
306
AN XY:
104294
show subpopulations
Gnomad AFR exome
AF:
0.000521
Gnomad AMR exome
AF:
0.000443
Gnomad ASJ exome
AF:
0.00398
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000383
Gnomad FIN exome
AF:
0.00819
Gnomad NFE exome
AF:
0.00455
Gnomad OTH exome
AF:
0.00223
GnomAD4 exome
AF:
0.00332
AC:
4684
AN:
1409026
Hom.:
10
Cov.:
29
AF XY:
0.00317
AC XY:
2215
AN XY:
698624
show subpopulations
Gnomad4 AFR exome
AF:
0.000579
Gnomad4 AMR exome
AF:
0.000301
Gnomad4 ASJ exome
AF:
0.00497
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000124
Gnomad4 FIN exome
AF:
0.00764
Gnomad4 NFE exome
AF:
0.00368
Gnomad4 OTH exome
AF:
0.00270
GnomAD4 genome
AF:
0.00234
AC:
355
AN:
151998
Hom.:
2
Cov.:
32
AF XY:
0.00248
AC XY:
184
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.000482
Gnomad4 AMR
AF:
0.000591
Gnomad4 ASJ
AF:
0.00549
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00565
Gnomad4 NFE
AF:
0.00360
Gnomad4 OTH
AF:
0.000950
Alfa
AF:
0.00312
Hom.:
1
Bravo
AF:
0.00189

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 19, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
5.7
DANN
Benign
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs189121824; hg19: chr12-85680614; API