4-48341963-C-T

Position:

• chr4-48341963-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

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=0.13038471).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAIN2	NM_020846.2	c.224C>T	p.Ser75Leu	missense_variant	1/8	ENST00000264313.11	NP_065897.1
SLAIN2	XM_005248121.4	c.224C>T	p.Ser75Leu	missense_variant	1/9		XP_005248178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAIN2	ENST00000264313.11	c.224C>T	p.Ser75Leu	missense_variant	1/8	1	NM_020846.2	ENSP00000264313.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

The c.224C>T (p.S75L) alteration is located in exon 1 (coding exon 1) of the SLAIN2 gene. This alteration results from a C to T substitution at nucleotide position 224, causing the serine (S) at amino acid position 75 to be replaced by a leucine (L). 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	0.081
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
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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.16
gMVP		0.14

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: chr4-48343980;