chr4-48341908-C-T

Variant names:

• chr4-48341908-C-T
• rs929716801
• NM_020846.2:c.169C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020846.2(SLAIN2):​c.169C>T​(p.Pro57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,508,650 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: SLAIN2 NM_020846.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.373
• Publications: 2 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13635218).

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>T	p.Pro57Ser	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>T	p.Pro57Ser	missense	Exon 1 of 8	ENSP00000264313.5	Q9P270
	SLAIN2	ENST00000512093.6	TSL:5	c.169C>T	p.Pro57Ser	missense	Exon 1 of 9	ENSP00000425923.2
	SLAIN2	ENST00000942830.1		c.169C>T	p.Pro57Ser	missense	Exon 1 of 8	ENSP00000612889.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000885 AC: 9 AN: 101724 AF XY: 0.000159

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000259

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000194 AC: 263 AN: 1356426 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 135 AN XY: 668540

African (AFR) AF: 0.0000369 AC: 1 AN: 27082

American (AMR) AF: 0.0000325 AC: 1 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: 0.0000133 AC: 1 AN: 75284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47186

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

European-Non Finnish (NFE) AF: 0.000240 AC: 255 AN: 1062216

Other (OTH) AF: 0.0000892 AC: 5 AN: 56040

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41470

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000138 Hom.: 0

Bravo AF: 0.0000831

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	0.064
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.92	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	-0.65	N
REVEL	Benign	0.051
Sift	Benign	0.33	T
Sift4G	Benign	0.20	T
Polyphen		0.0010	B
Vest4		0.28
MutPred		0.28		Gain of sheet (P = 0.0221)
MVP		0.043
MPC		0.65
ClinPred		0.066	T
GERP RS		3.3
PromoterAI		0.32	Neutral
Varity_R		0.057
gMVP		0.28
Mutation Taster		=74/26	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;