rs776193218

Variant names:

• chr4-48341878-G-C
• rs776193218
• NM_020846.2:c.139G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020846.2(SLAIN2):​c.139G>C​(p.Gly47Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000353 in 1,517,132 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: SLAIN2 NM_020846.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.809
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0059365034).

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.139G>C	p.Gly47Arg	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.139G>C	p.Gly47Arg	missense	Exon 1 of 8	ENSP00000264313.5	Q9P270
	SLAIN2	ENST00000512093.6	TSL:5	c.139G>C	p.Gly47Arg	missense	Exon 1 of 9	ENSP00000425923.2
	SLAIN2	ENST00000942830.1		c.139G>C	p.Gly47Arg	missense	Exon 1 of 8	ENSP00000612889.1

Frequencies

GnomAD3 genomes AF: 0.000611 AC: 93 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.000681 AC: 76 AN: 111566 AF XY: 0.000584

Gnomad AFR exome AF: 0.000435

Gnomad AMR exome AF: 0.00161

Gnomad ASJ exome AF: 0.00298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000436

Gnomad OTH exome AF: 0.00159

GnomAD4 exome AF: 0.000325 AC: 443 AN: 1364808 Hom.: 0 Cov.: 33 AF XY: 0.000314 AC XY: 211 AN XY: 672734

African (AFR) AF: 0.000253 AC: 7 AN: 27664

American (AMR) AF: 0.00167 AC: 54 AN: 32374

Ashkenazi Jewish (ASJ) AF: 0.00311 AC: 74 AN: 23776

East Asian (EAS) AF: 0.0000318 AC: 1 AN: 31444

South Asian (SAS) AF: 0.00 AC: 0 AN: 76252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47604

Middle Eastern (MID) AF: 0.00224 AC: 9 AN: 4012

European-Non Finnish (NFE) AF: 0.000227 AC: 242 AN: 1065296

Other (OTH) AF: 0.000993 AC: 56 AN: 56386

GnomAD4 genome AF: 0.000604 AC: 92 AN: 152324 Hom.: 0 Cov.: 33 AF XY: 0.000591 AC XY: 44 AN XY: 74482

African (AFR) AF: 0.000769 AC: 32 AN: 41590

American (AMR) AF: 0.00176 AC: 27 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68014

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.000655 Hom.: 0

Bravo AF: 0.000805

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000303 AC: 18

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	0.17
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.60
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.81
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.040	N
REVEL	Benign	0.065
Sift	Benign	0.48	T
Sift4G	Benign	0.57	T
Polyphen		0.0010	B
Vest4		0.13
MVP		0.043
MPC		0.25
ClinPred		0.025	T
GERP RS		3.4
PromoterAI		-0.061	Neutral
Varity_R		0.034
gMVP		0.21
Mutation Taster		=92/8	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: rs776193218; hg19: chr4-48343895;