20-10622969-G-T

Variant names:

• chr20-10622969-G-T
• rs763265831
• NM_001009608.3:c.817G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009608.3(SLX4IP):​c.817G>T​(p.Val273Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. V273I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLX4IP NM_001009608.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20602006).

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.817G>T	p.Val273Phe	missense	Exon 8 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.817G>T	p.Val273Phe	missense	Exon 8 of 8	ENSP00000335557.5	Q5VYV7
	SLX4IP	ENST00000931374.1		c.727G>T	p.Val243Phe	missense	Exon 7 of 7	ENSP00000601433.1
	SLX4IP	ENST00000488816.1	TSL:5	n.166-13327G>T		intron	N/A	ENSP00000432784.1	H0YD23

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251362 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.6
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.10
Sift	Benign	0.041	D
Sift4G	Uncertain	0.048	D
Polyphen		0.97	D
Vest4		0.16
MutPred		0.10		Loss of glycosylation at S269 (P = 0.1581)
MVP		0.62
MPC		0.50
ClinPred		0.80	D
GERP RS		5.1
Varity_R		0.11
gMVP		0.12
Mutation Taster		=90/10	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: rs763265831; hg19: chr20-10603617;