4-48341963-C-T

Variant names:

• chr4-48341963-C-T
• NM_020846.2:c.224C>T

Variant summary

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

The NM_020846.2(SLAIN2):​c.224C>T​(p.Ser75Leu) 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. 13/21 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. S75A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLAIN2 NM_020846.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98
• Publications: 0 publications found

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]

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=0.13038471).

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.224C>T	p.Ser75Leu	missense	Exon 1 of 8	NP_065897.1	A0A024R9T6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLAIN2	ENST00000264313.11	TSL:1 MANE Select	c.224C>T	p.Ser75Leu	missense	Exon 1 of 8	ENSP00000264313.5	Q9P270
	SLAIN2	ENST00000512093.6	TSL:5	c.224C>T	p.Ser75Leu	missense	Exon 1 of 9	ENSP00000425923.2
	SLAIN2	ENST00000942830.1		c.224C>T	p.Ser75Leu	missense	Exon 1 of 8	ENSP00000612889.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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	0.081
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.62	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Benign	0.17	T
Sift4G	Benign	0.31	T
Polyphen		0.021	B
Vest4		0.12
MutPred		0.29		Gain of glycosylation at S72 (P = 0.0155)
MVP		0.043
MPC		0.18
ClinPred		0.28	T
GERP RS		4.3
PromoterAI		-0.0070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.16
gMVP		0.14
Mutation Taster		=80/20	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

hg19: chr4-48343980;