20-10622766-G-T

Variant names:

• chr20-10622766-G-T
• NM_001009608.3:c.614G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009608.3(SLX4IP):​c.614G>T​(p.Arg205Met) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLX4IP NM_001009608.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092321545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4IP	NM_001009608.3	c.614G>T	p.Arg205Met	missense_variant	Exon 8 of 8	ENST00000334534.10	NP_001009608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLX4IP	ENST00000334534.10	c.614G>T	p.Arg205Met	missense_variant	Exon 8 of 8	1	NM_001009608.3	ENSP00000335557.5
SLX4IP	ENST00000488816.1	n.166-13530G>T		intron_variant	Intron 2 of 3	5		ENSP00000432784.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.614G>T (p.R205M) alteration is located in exon 8 (coding exon 7) of the SLX4IP gene. This alteration results from a G to T substitution at nucleotide position 614, causing the arginine (R) at amino acid position 205 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.10
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.014	D
Polyphen		0.37	B
Vest4		0.27
MutPred		0.12		Loss of MoRF binding (P = 0.0974);
MVP		0.37
MPC		0.40
ClinPred		0.52	D
GERP RS		2.4
Varity_R		0.088
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-10603414;