Genetic Variant SALL4:p.Val1027Val (chr20-51784346-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS2

The NM_020436.5(SALL4):c.3081G>A(p.Val1027Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,892 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: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SALL4
NM_020436.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.904

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]

SALL4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 20-51784346-C-T is Benign according to our data. Variant chr20-51784346-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3661145.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.904 with no splicing effect.

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL4	NM_020436.5 link	c.3081G>A	p.Val1027Val	synonymous_variant	Exon 4 of 4	ENST00000217086.9	NP_065169.1	Q9UJQ4-1
SALL4	NM_001318031.2 link	c.1770G>A	p.Val590Val	synonymous_variant	Exon 4 of 4		NP_001304960.1	Q9UJQ4-2
SALL4	XM_047440318.1 link	c.2775G>A	p.Val925Val	synonymous_variant	Exon 4 of 4		XP_047296274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SALL4	ENST00000217086.9 link	c.3081G>A	p.Val1027Val	synonymous_variant	Exon 4 of 4	1	NM_020436.5	ENSP00000217086.4	Q9UJQ4-1
SALL4	ENST00000395997.3 link	c.1770G>A	p.Val590Val	synonymous_variant	Exon 4 of 4	1		ENSP00000379319.3	Q9UJQ4-2
SALL4	ENST00000371539.7 link	c.750G>A	p.Val250Val	synonymous_variant	Exon 3 of 3	1		ENSP00000360594.3	Q6Y8G5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251494

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135922

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Duane-radial ray syndrome

Benign:1

Nov 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.6

DANN

Benign

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over