rs1371942771

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-29457656-C-A
• chr16-29457656-C-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>A​(p.Pro203Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P203S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000010 (0 hom., cov: 15)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLX1B NM_024044.5 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.18753904).

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>A	p.Pro203Thr	missense	Exon 4 of 6	NP_076949.1
	SLX1B	NM_001400286.1		c.601C>A	p.Pro201Thr	missense	Exon 4 of 6	NP_001387215.1
	SLX1B	NM_178044.4		c.265C>A	p.Pro89Thr	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>A	p.Pro203Thr	missense	Exon 4 of 6	ENSP00000328940.5	Q9BQ83-1
	SLX1B	ENST00000351581.4	TSL:1	c.265C>A	p.Pro89Thr	missense	Exon 3 of 5	ENSP00000335316.4	Q9BQ83-2
	SLX1B	ENST00000856228.1		c.493C>A	p.Pro165Thr	missense	Exon 4 of 6	ENSP00000526287.1

Frequencies

GnomAD3 genomes AF: 0.0000101 AC: 1 AN: 99128 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.0000300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000211 AC: 2 AN: 947212 Hom.: 0 Cov.: 14 AF XY: 0.00000214 AC XY: 1 AN XY: 468140

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

African (AFR) AF: 0.0000360 AC: 1 AN: 27782

American (AMR) AF: 0.00 AC: 0 AN: 20738

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: 0.00000137 AC: 1 AN: 730250

Other (OTH) AF: 0.00 AC: 0 AN: 40434

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000101 AC: 1 AN: 99128 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 46848

African (AFR) AF: 0.0000300 AC: 1 AN: 33358

American (AMR) AF: 0.00 AC: 0 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

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.94
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.4
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.045
Sift	Benign	0.11	T
Sift4G	Benign	0.35	T
Vest4		0.25
MutPred		0.36		Gain of sheet (P = 0.0266)
MVP		0.093
MPC		3.4
ClinPred		0.96	D
GERP RS		2.5
gMVP		0.54

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;