4-48342020-C-T

Variant names:

• chr4-48342020-C-T
• rs1714722510
• NM_020846.2:c.281C>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.281C>T​(p.Ala94Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,261,070 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A94S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: SLAIN2 NM_020846.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84
• 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=0.09962261).

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.281C>T	p.Ala94Val	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.281C>T	p.Ala94Val	missense	Exon 1 of 8	ENSP00000264313.5	Q9P270
	SLAIN2	ENST00000512093.6	TSL:5	c.281C>T	p.Ala94Val	missense	Exon 1 of 9	ENSP00000425923.2
	SLAIN2	ENST00000942830.1		c.281C>T	p.Ala94Val	missense	Exon 1 of 8	ENSP00000612889.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.93e-7 AC: 1 AN: 1261070 Hom.: 0 Cov.: 33 AF XY: 0.00000163 AC XY: 1 AN XY: 615326

African (AFR) AF: 0.00 AC: 0 AN: 24386

American (AMR) AF: 0.00 AC: 0 AN: 12840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18346

East Asian (EAS) AF: 0.00 AC: 0 AN: 27822

South Asian (SAS) AF: 0.0000168 AC: 1 AN: 59464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4584

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1020808

Other (OTH) AF: 0.00 AC: 0 AN: 51802

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	0.089
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.8
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.081
Sift	Benign	0.26	T
Sift4G	Benign	0.51	T
Polyphen		0.013	B
Vest4		0.21
MutPred		0.16		Gain of glycosylation at T95 (P = 0.0092)
MVP		0.068
MPC		0.24
ClinPred		0.19	T
GERP RS		3.9
PromoterAI		0.14	Neutral
Varity_R		0.11
gMVP		0.25
Mutation Taster		=87/13	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

dbSNP: rs1714722510; hg19: chr4-48344037;