Genetic Variant NM_006425.5:c.1461G>A (chr5-160404812-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006425.5(SLU7):c.1461G>A(p.Met487Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,449,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M487V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLU7
NM_006425.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

Publications

0 publications found

Variant links:

Genes affected

SLU7 (HGNC:16939): (SLU7 homolog, splicing factor) Pre-mRNA splicing occurs in two sequential transesterification steps. The protein encoded by this gene is a splicing factor that has been found to be essential during the second catalytic step in the pre-mRNA splicing process. It associates with the spliceosome and contains a zinc knuckle motif that is found in other splicing factors and is involved in protein-nucleic acid and protein-protein interactions. [provided by RefSeq, Jul 2008]

SLU7 links:

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ACMG classification

Classification was made for transcript

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=0.13574731).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006425.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLU7	NM_006425.5	MANE Select	c.1461G>A	p.Met487Ile	missense	Exon 14 of 16	NP_006416.3
SLU7	NM_001364517.2		c.1506G>A	p.Met502Ile	missense	Exon 14 of 16	NP_001351446.1
SLU7	NM_001364522.2		c.1491G>A	p.Met497Ile	missense	Exon 14 of 16	NP_001351451.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLU7	ENST00000297151.9	TSL:1 MANE Select	c.1461G>A	p.Met487Ile	missense	Exon 14 of 16	ENSP00000297151.4	O95391
SLU7	ENST00000855629.1		c.1461G>A	p.Met487Ile	missense	Exon 15 of 17	ENSP00000525688.1
SLU7	ENST00000938507.1		c.1461G>A	p.Met487Ile	missense	Exon 14 of 16	ENSP00000608566.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1449922

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722160

show subpopulations

African (AFR)

AF:

0.0000602

AC:

AN:

33232

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26056

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.00

AC:

AN:

85978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

9.08e-7

AC:

AN:

1101154

Other (OTH)

AF:

0.00

AC:

AN:

60008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.023

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.010

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

1.5

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.070

REVEL

Benign

0.051

Sift

Benign

0.28

Sift4G

Benign

0.27

Polyphen

0.0

Vest4

0.41

MutPred

0.24

Loss of helix (P = 0.079)

MVP

0.42

MPC

0.16

ClinPred

0.35

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.083

gMVP

0.20

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over