chr4-48342060-C-G

Variant names:

• chr4-48342060-C-G
• rs1300276183
• NM_020846.2:c.321C>G

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.321C>G​(p.Asp107Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 1,229,584 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (1 hom.)
• Consequence: SLAIN2 NM_020846.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• 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=0.17878127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAIN2	NM_020846.2	c.321C>G	p.Asp107Glu	missense_variant	Exon 1 of 8	ENST00000264313.11	NP_065897.1
SLAIN2	XM_005248121.4	c.321C>G	p.Asp107Glu	missense_variant	Exon 1 of 9		XP_005248178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLAIN2	ENST00000264313.11	c.321C>G	p.Asp107Glu	missense_variant	Exon 1 of 8	1	NM_020846.2	ENSP00000264313.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000163 AC: 2 AN: 1229584 Hom.: 1 Cov.: 33 AF XY: 0.00000335 AC XY: 2 AN XY: 596956

African (AFR) AF: 0.00 AC: 0 AN: 23838

American (AMR) AF: 0.00 AC: 0 AN: 10252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17268

East Asian (EAS) AF: 0.00 AC: 0 AN: 27488

South Asian (SAS) AF: 0.00 AC: 0 AN: 54482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4356

European-Non Finnish (NFE) AF: 0.00000198 AC: 2 AN: 1007778

Other (OTH) AF: 0.00 AC: 0 AN: 50716

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		1.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.045
Sift	Benign	0.059	T
Sift4G	Benign	0.11	T
Polyphen		0.21	B
Vest4		0.32
MutPred		0.35		Gain of sheet (P = 0.0043);
MVP		0.043
MPC		0.76
ClinPred		0.91	D
GERP RS		1.2
Varity_R		0.33
gMVP		0.40
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: rs1300276183; hg19: chr4-48344077;