20-51784019-C-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020436.5(SALL4):c.*245_*246insTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 487,208 control chromosomes in the GnomAD database, including 301 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (183 hom., cov: 31)
  • Exomes 𝑓: 0.044 (118 hom.)
• Consequence: SALL4 NM_020436.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 20-51784019-C-CAA is Benign according to our data. Variant chr20-51784019-C-CAA is described in ClinVar as [Benign]. Clinvar id is 1233920.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL4	NM_020436.5	c.*245_*246insTT		3_prime_UTR_variant	4/4	ENST00000217086.9
SALL4	NM_001318031.2	c.*245_*246insTT		3_prime_UTR_variant	4/4
SALL4	XM_047440318.1	c.*245_*246insTT		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL4	ENST00000217086.9	c.*245_*246insTT		3_prime_UTR_variant	4/4	1	NM_020436.5	P1
SALL4	ENST00000371539.7			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7004 AN: 149008 Hom.: 183 Cov.: 31

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0255

Gnomad EAS AF: 0.0336

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0591

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0640

Gnomad OTH AF: 0.0532

GnomAD4 exome AF: 0.0443 AC: 14973 AN: 338082 Hom.: 118 Cov.: 3 AF XY: 0.0435 AC XY: 7874 AN XY: 180832

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.0308

Gnomad4 ASJ exome AF: 0.0253

Gnomad4 EAS exome AF: 0.0390

Gnomad4 SAS exome AF: 0.0280

Gnomad4 FIN exome AF: 0.0471

Gnomad4 NFE exome AF: 0.0512

Gnomad4 OTH exome AF: 0.0445

GnomAD4 genome AF: 0.0470 AC: 7002 AN: 149126 Hom.: 183 Cov.: 31 AF XY: 0.0459 AC XY: 3336 AN XY: 72652

Gnomad4 AFR AF: 0.0218

Gnomad4 AMR AF: 0.0418

Gnomad4 ASJ AF: 0.0255

Gnomad4 EAS AF: 0.0337

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.0591

Gnomad4 NFE AF: 0.0640

Gnomad4 OTH AF: 0.0521

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 12, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60718711; hg19: chr20-50400558;