rs770717675

Variant names:

• chr20-10560773-G-A
• rs770717675
• NM_001009608.3:c.191G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001009608.3(SLX4IP):​c.191G>A​(p.Arg64Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,456,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SLX4IP NM_001009608.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.371
• Publications: 1 publications found

Genes affected

SLX4IP (HGNC:16225): (SLX4 interacting protein)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03027603).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009608.3. 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
	SLX4IP	NM_001009608.3	MANE Select	c.191G>A	p.Arg64Lys	missense	Exon 4 of 8	NP_001009608.1	Q5VYV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX4IP	ENST00000334534.10	TSL:1 MANE Select	c.191G>A	p.Arg64Lys	missense	Exon 4 of 8	ENSP00000335557.5	Q5VYV7
	SLX4IP	ENST00000931374.1		c.101G>A	p.Arg34Lys	missense	Exon 3 of 7	ENSP00000601433.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000323 AC: 8 AN: 247362 AF XY: 0.0000224

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000443

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1456110 Hom.: 0 Cov.: 30 AF XY: 0.00000690 AC XY: 5 AN XY: 724394

African (AFR) AF: 0.00 AC: 0 AN: 33218

American (AMR) AF: 0.00 AC: 0 AN: 43670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.000458 AC: 18 AN: 39334

South Asian (SAS) AF: 0.00 AC: 0 AN: 85322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109368

Other (OTH) AF: 0.0000166 AC: 1 AN: 60140

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

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	0.075
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.70
DANN	Benign	0.57
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.025	N
PhyloP100		0.37
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.028
Sift	Benign	0.28	T
Sift4G	Benign	0.83	T
Polyphen		0.0020	B
Vest4		0.14
MutPred		0.26		Gain of ubiquitination at R64 (P = 0.0128)
MVP		0.13
MPC		0.090
ClinPred		0.012	T
GERP RS		-3.9
Varity_R		0.069
gMVP		0.16
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: rs770717675; hg19: chr20-10541421; COSMIC: COSV105893022;