16-29457979-C-G

Variant names:

• chr16-29457979-C-G
• NM_024044.5:c.762C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024044.5(SLX1B):​c.762C>G​(p.Asp254Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLX1B NM_024044.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0260
• Publications: 0 publications found

Genes affected

SLX1B (HGNC:28748): (SLX1 homolog B, structure-specific endonuclease subunit) This gene encodes a protein that is an important regulator of genome stability. The protein represents the catalytic subunit of the SLX1-SLX4 structure-specific endonuclease, which can resolve DNA secondary structures that are formed during repair and recombination processes. Two identical copies of this gene are located on the p arm of chromosome 16 due to a segmental duplication; this record represents the more telomeric copy. Alternative splicing results in multiple transcript variants. Read-through transcription also occurs between this gene and the downstream SULT1A4 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 4) gene. [provided by RefSeq, Nov 2010]

SLX1B-SULT1A4 (HGNC:48353): (SLX1B-SULT1A4 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring SLX1B (SLX1 structure-specific endonuclease subunit homolog B) and SULT1A4 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 4) genes on the short arm of chromosome 16. A duplicate read-through locus also exists between the SLX1A and SULT1A3 genes located approximately 730 kb downstream on the same chromosome. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10128063).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024044.5. 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
	SLX1B	NM_024044.5	MANE Select	c.762C>G	p.Asp254Glu	missense	Exon 5 of 6	NP_076949.1
	SLX1B	NM_001400286.1		c.756C>G	p.Asp252Glu	missense	Exon 5 of 6	NP_001387215.1
	SLX1B	NM_178044.4		c.420C>G	p.Asp140Glu	missense	Exon 4 of 5	NP_835145.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX1B	ENST00000330181.10	TSL:1 MANE Select	c.762C>G	p.Asp254Glu	missense	Exon 5 of 6	ENSP00000328940.5	Q9BQ83-1
	SLX1B	ENST00000351581.4	TSL:1	c.420C>G	p.Asp140Glu	missense	Exon 4 of 5	ENSP00000335316.4	Q9BQ83-2
	SLX1B	ENST00000856228.1		c.648C>G	p.Asp216Glu	missense	Exon 5 of 6	ENSP00000526287.1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000266 AC: 3 AN: 1128800 Hom.: 0 Cov.: 21 AF XY: 0.00000352 AC XY: 2 AN XY: 568354

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31044

American (AMR) AF: 0.00 AC: 0 AN: 35958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20958

East Asian (EAS) AF: 0.00 AC: 0 AN: 26078

South Asian (SAS) AF: 0.00 AC: 0 AN: 69856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4028

European-Non Finnish (NFE) AF: 0.00000354 AC: 3 AN: 847668

Other (OTH) AF: 0.00 AC: 0 AN: 47768

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 18

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.7
DANN	Benign	0.92
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.026
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.0090
Sift	Benign	0.30	T
Sift4G	Benign	0.37	T
Vest4		0.056
MutPred		0.32		Loss of loop (P = 0.0389)
MVP		0.068
MPC		1.8
ClinPred		0.082	T
GERP RS		-2.2
gMVP		0.32

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

Other links and lift over

hg19: chr16-29469300;