chr16-29457656-C-T

Variant names:

• chr16-29457656-C-T
• rs1371942771
• NM_024044.5:c.607C>T

Variant summary

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

The NM_024044.5(SLX1B):​c.607C>T​(p.Pro203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 15)
  • Exomes 𝑓: 0.000023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLX1B NM_024044.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• 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=0.12426537).

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.607C>T	p.Pro203Ser	missense	Exon 4 of 6	NP_076949.1
	SLX1B	NM_001400286.1		c.601C>T	p.Pro201Ser	missense	Exon 4 of 6	NP_001387215.1
	SLX1B	NM_178044.4		c.265C>T	p.Pro89Ser	missense	Exon 3 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.607C>T	p.Pro203Ser	missense	Exon 4 of 6	ENSP00000328940.5	Q9BQ83-1
	SLX1B	ENST00000351581.4	TSL:1	c.265C>T	p.Pro89Ser	missense	Exon 3 of 5	ENSP00000335316.4	Q9BQ83-2
	SLX1B	ENST00000856228.1		c.493C>T	p.Pro165Ser	missense	Exon 4 of 6	ENSP00000526287.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 13 AN: 99128 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00159

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000534 AC: 3 AN: 56198 AF XY: 0.0000701

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000455

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000232 AC: 22 AN: 947198 Hom.: 0 Cov.: 14 AF XY: 0.0000235 AC XY: 11 AN XY: 468134

⚠️ 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: 27782

American (AMR) AF: 0.000241 AC: 5 AN: 20734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15524

East Asian (EAS) AF: 0.00 AC: 0 AN: 18604

South Asian (SAS) AF: 0.00 AC: 0 AN: 54372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2758

European-Non Finnish (NFE) AF: 0.0000219 AC: 16 AN: 730242

Other (OTH) AF: 0.0000247 AC: 1 AN: 40432

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000694869), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000131 AC: 13 AN: 99128 Hom.: 0 Cov.: 15 AF XY: 0.000149 AC XY: 7 AN XY: 46848

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

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.00159 AC: 13 AN: 8198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2088

East Asian (EAS) AF: 0.00 AC: 0 AN: 1094

South Asian (SAS) AF: 0.00 AC: 0 AN: 2078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44720

Other (OTH) AF: 0.00 AC: 0 AN: 1186

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000140282), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.98
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
PhyloP100		1.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.028
Sift	Benign	0.062	T
Sift4G	Benign	0.13	T
Vest4		0.30
MutPred		0.30		Gain of sheet (P = 0.0344)
MVP		0.11
MPC		3.3
ClinPred		0.54	D
GERP RS		2.5
gMVP		0.57
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs1371942771; hg19: chr16-29468977;