4-48341908-C-G

Variant names:

• chr4-48341908-C-G
• rs929716801
• NM_020846.2:c.169C>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.169C>G​(p.Pro57Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,428 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P57S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: SLAIN2 NM_020846.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373
• 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=0.14362118).

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.169C>G	p.Pro57Ala	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.169C>G	p.Pro57Ala	missense	Exon 1 of 8	ENSP00000264313.5	Q9P270
	SLAIN2	ENST00000512093.6	TSL:5	c.169C>G	p.Pro57Ala	missense	Exon 1 of 9	ENSP00000425923.2
	SLAIN2	ENST00000942830.1		c.169C>G	p.Pro57Ala	missense	Exon 1 of 8	ENSP00000612889.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356428 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 668540

African (AFR) AF: 0.00 AC: 0 AN: 27082

American (AMR) AF: 0.00 AC: 0 AN: 30780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23294

East Asian (EAS) AF: 0.00 AC: 0 AN: 30532

South Asian (SAS) AF: 0.00 AC: 0 AN: 75284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4012

European-Non Finnish (NFE) AF: 9.41e-7 AC: 1 AN: 1062216

Other (OTH) AF: 0.00 AC: 0 AN: 56040

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.37
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.043
Sift	Benign	0.39	T
Sift4G	Benign	0.12	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.29		Gain of glycosylation at S58 (P = 0.0331)
MVP		0.043
MPC		0.58
ClinPred		0.10	T
GERP RS		3.3
PromoterAI		0.039	Neutral
Varity_R		0.063
gMVP		0.19
Mutation Taster		=73/27	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: rs929716801; hg19: chr4-48343925;