NM_001014999.3:c.738C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

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

• BP4: Computational evidence support a benign effect (REVEL=0.022).
• 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 VariationId is 2646381.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.678 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014999.3. 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
	SLX1A	NM_001014999.3	MANE Select	c.738C>T	p.Asp246Asp	synonymous	Exon 5 of 6	NP_001014999.1	Q9BQ83-1
	SLX1A	NM_001015000.2		c.396C>T	p.Asp132Asp	synonymous	Exon 4 of 5	NP_001015000.1	Q9BQ83-2
	SLX1A-SULT1A3	NR_037608.1		n.857C>T		non_coding_transcript_exon	Exon 4 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX1A	ENST00000251303.11	TSL:1 MANE Select	c.738C>T	p.Asp246Asp	synonymous	Exon 5 of 6	ENSP00000251303.7	Q9BQ83-1
	SLX1A	ENST00000345535.9	TSL:1	c.396C>T	p.Asp132Asp	synonymous	Exon 4 of 5	ENSP00000333945.4	Q9BQ83-2
	SLX1A	ENST00000941762.1		c.795C>T	p.Asp265Asp	synonymous	Exon 5 of 6	ENSP00000611821.1

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

GnomAD2 exomes AF: 0.00249 AC: 468 AN: 187740 AF XY: 0.00295

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 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

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

African (AFR) AF: 0.000225 AC: 4 AN: 17744

American (AMR) AF: 0.000576 AC: 24 AN: 41634

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 598 AN: 21138

East Asian (EAS) AF: 0.00 AC: 0 AN: 38852

South Asian (SAS) AF: 0.00807 AC: 603 AN: 74688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49018

Middle Eastern (MID) AF: 0.00545 AC: 22 AN: 4036

European-Non Finnish (NFE) AF: 0.000426 AC: 298 AN: 699222

Other (OTH) AF: 0.00338 AC: 149 AN: 44124

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

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

African (AFR) AF: 0.000122 AC: 3 AN: 24516

American (AMR) AF: 0.00322 AC: 41 AN: 12740

Ashkenazi Jewish (ASJ) AF: 0.0330 AC: 93 AN: 2822

East Asian (EAS) AF: 0.00 AC: 0 AN: 4894

South Asian (SAS) AF: 0.00812 AC: 33 AN: 4066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8564

Middle Eastern (MID) AF: 0.00833 AC: 2 AN: 240

European-Non Finnish (NFE) AF: 0.000674 AC: 36 AN: 53438

Other (OTH) AF: 0.00303 AC: 5 AN: 1648

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00135 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	8.6
DANN	Benign	0.93
PhyloP100		0.68
Mutation Taster		=100/0	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: rs201044062; hg19: chr16-30208618; COSMIC: COSV105862956; COSMIC: COSV105862956;