7-66994329-G-C

Variant names:

• chr7-66994329-G-C
• NM_016038.4:c.141C>G
• SBDS p.Leu47Leu

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_016038.4(SBDS):​c.141C>G​(p.Leu47Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L47L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SBDS NM_016038.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.801
• Publications: 0 publications found

Genes affected

SBDS (HGNC:19440): (SBDS ribosome maturation factor) This gene encodes a highly conserved protein that plays an essential role in ribosome biogenesis. The encoded protein interacts with elongation factor-like GTPase 1 to disassociate eukaryotic initiation factor 6 from the late cytoplasmic pre-60S ribosomal subunit allowing assembly of the 80S subunit. Mutations within this gene are associated with the autosomal recessive disorder Shwachman-Bodian-Diamond syndrome. This gene has a closely linked pseudogene that is distally located. [provided by RefSeq, Jan 2017]

SBDS Gene-Disease associations (from GenCC):

• Shwachman-Diamond syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Shwachman-Diamond syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-66994329-G-C is Benign according to our data. Variant chr7-66994329-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 4630224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.801 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016038.4. 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
	SBDS	NM_016038.4	MANE Select	c.141C>G	p.Leu47Leu	synonymous	Exon 2 of 5	NP_057122.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBDS	ENST00000246868.7	TSL:1 MANE Select	c.141C>G	p.Leu47Leu	synonymous	Exon 2 of 5	ENSP00000246868.2	Q9Y3A5
	SBDS	ENST00000697866.1		c.-178C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000513464.1	A0A8V8TLC6
	SBDS	ENST00000697897.1		c.141C>G	p.Leu47Leu	synonymous	Exon 3 of 6	ENSP00000513469.1	Q9Y3A5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.6
DANN	Benign	0.73
PhyloP100		-0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-66459316;