Genetic Variant SLAIN2:p.Pro49Leu (chr4-48341885-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_020846.2(SLAIN2):c.146C>T(p.Pro49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,361,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. P49R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

SLAIN2
NM_020846.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

Publications

0 publications found

Variant links:

Genes affected

SLAIN2 (HGNC:29282): (SLAIN motif family member 2) Involved in cytoplasmic microtubule organization; microtubule nucleation; and positive regulation of microtubule polymerization. Located in centrosome and cytosol. Colocalizes with microtubule plus-end. [provided by Alliance of Genome Resources, Apr 2022]

SLAIN2 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=0.17003062).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020846.2. 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
	SLAIN2	NM_020846.2	MANE Select	c.146C>T	p.Pro49Leu	missense	Exon 1 of 8	NP_065897.1	A0A024R9T6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLAIN2	ENST00000264313.11	TSL:1 MANE Select	c.146C>T	p.Pro49Leu	missense	Exon 1 of 8	ENSP00000264313.5	Q9P270
SLAIN2	ENST00000512093.6	TSL:5	c.146C>T	p.Pro49Leu	missense	Exon 1 of 9	ENSP00000425923.2
SLAIN2	ENST00000942830.1		c.146C>T	p.Pro49Leu	missense	Exon 1 of 8	ENSP00000612889.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.34e-7

AC:

AN:

1361624

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

671122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27470

American (AMR)

AF:

0.00

AC:

AN:

31874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23584

East Asian (EAS)

AF:

0.00

AC:

AN:

31108

South Asian (SAS)

AF:

0.00

AC:

AN:

75862

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3992

European-Non Finnish (NFE)

AF:

9.40e-7

AC:

AN:

1064068

Other (OTH)

AF:

0.00

AC:

AN:

56248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.030

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.7

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.2

REVEL

Benign

0.065

Sift

Benign

0.051

Sift4G

Benign

0.21

Polyphen

0.0030

Vest4

0.11

MutPred

0.20

Loss of loop (P = 0.0288)

MVP

0.043

MPC

0.21

ClinPred

0.13

GERP RS

4.2

PromoterAI

0.014

Neutral

(source)

Varity_R

0.070

gMVP

0.38

Mutation Taster

=70/30

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