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GeneBe

20-51784331-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020436.5(SALL4):c.3096T>C(p.Ala1032=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000285 in 1,614,190 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

SALL4
NM_020436.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.477
Variant links:
Genes affected
SALL4 (HGNC:15924): (spalt like transcription factor 4) This gene encodes a zinc finger transcription factor thought to play a role in the development of abducens motor neurons. Defects in this gene are a cause of Duane-radial ray syndrome (DRRS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-51784331-A-G is Benign according to our data. Variant chr20-51784331-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 767016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-51784331-A-G is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.477 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SALL4NM_020436.5 linkuse as main transcriptc.3096T>C p.Ala1032= synonymous_variant 4/4 ENST00000217086.9
SALL4NM_001318031.2 linkuse as main transcriptc.1785T>C p.Ala595= synonymous_variant 4/4
SALL4XM_047440318.1 linkuse as main transcriptc.2790T>C p.Ala930= synonymous_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SALL4ENST00000217086.9 linkuse as main transcriptc.3096T>C p.Ala1032= synonymous_variant 4/41 NM_020436.5 P1Q9UJQ4-1
SALL4ENST00000395997.3 linkuse as main transcriptc.1785T>C p.Ala595= synonymous_variant 4/41 Q9UJQ4-2
SALL4ENST00000371539.7 linkuse as main transcriptc.765T>C p.Ala255= synonymous_variant 3/31

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000171
AC:
26
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
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:
0.000323
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000219
AC:
55
AN:
251494
Hom.:
0
AF XY:
0.000235
AC XY:
32
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000413
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000297
AC:
434
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.000285
AC XY:
207
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000157
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:
0.000371
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000171
AC:
26
AN:
152298
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000323
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000327
Hom.:
0
Bravo
AF:
0.000170
EpiCase
AF:
0.000491
EpiControl
AF:
0.000711

ClinVar

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

Submissions by phenotype

Duane-radial ray syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeMay 16, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
Cadd
Benign
0.19
Dann
Benign
0.37

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.

Other links and lift over

dbSNP: rs370319434; hg19: chr20-50400870; API