16-30197297-C-T

Variant names:

• chr16-30197297-C-T
• rs201044062
• NM_001014999.3:c.738C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001014999.3(SLX1A):​c.738C>T​(p.Asp246Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0017 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLX1A NM_001014999.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.678

Genes affected

SLX1A (HGNC:20922): (SLX1 homolog A, 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 centromeric copy. Alternative splicing results in multiple transcript variants. Read-through transcription also occurs between this gene and the downstream SULT1A3 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3) gene. [provided by RefSeq, Nov 2010]

SLX1A-SULT1A3 (HGNC:44437): (SLX1A-SULT1A3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring SLX1A (SLX1 structure-specific endonuclease subunit homolog A) and SULT1A3 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3) genes on the short arm of chromosome 16. A duplicate read-through locus also exists between the SLX1B and SULT1A4 genes located approximately 730 kb upstream 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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 16-30197297-C-T is Benign according to our data. Variant chr16-30197297-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2646381.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.678 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX1A	NM_001014999.3	c.738C>T	p.Asp246Asp	synonymous_variant	Exon 5 of 6	ENST00000251303.11	NP_001014999.1
SLX1A	NM_001015000.2	c.396C>T	p.Asp132Asp	synonymous_variant	Exon 4 of 5		NP_001015000.1
SLX1A-SULT1A3	NR_037608.1	n.857C>T		non_coding_transcript_exon_variant	Exon 4 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLX1A	ENST00000251303.11	c.738C>T	p.Asp246Asp	synonymous_variant	Exon 5 of 6	1	NM_001014999.3	ENSP00000251303.7

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 214 AN: 113622 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00322

Gnomad ASJ AF: 0.0330

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00833

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00769

Gnomad NFE AF: 0.000674

Gnomad OTH AF: 0.00307

GnomAD3 exomes AF: 0.00249 AC: 468 AN: 187740 Hom.: 0 AF XY: 0.00295 AC XY: 299 AN XY: 101446

Gnomad AFR exome AF: 0.000333

Gnomad AMR exome AF: 0.000546

Gnomad ASJ exome AF: 0.0267

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00792

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000756

Gnomad OTH exome AF: 0.00233

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00171 AC: 1698 AN: 990456 Hom.: 6 Cov.: 16 AF XY: 0.00204 AC XY: 1030 AN XY: 505992

Gnomad4 AFR exome AF: 0.000225

Gnomad4 AMR exome AF: 0.000576

Gnomad4 ASJ exome AF: 0.0283

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00807

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000426

Gnomad4 OTH exome AF: 0.00338

GnomAD4 genome AF: 0.00187 AC: 213 AN: 113654 Hom.: 0 Cov.: 17 AF XY: 0.00225 AC XY: 125 AN XY: 55492

Gnomad4 AFR AF: 0.000122

Gnomad4 AMR AF: 0.00322

Gnomad4 ASJ AF: 0.0330

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00812

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000674

Gnomad4 OTH AF: 0.00303

Alfa AF: 0.00135 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLX1A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	8.6
DANN	Benign	0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs201044062; hg19: chr16-30208618; COSMIC: COSV105862956; COSMIC: COSV105862956;