4-48341768-C-T

Position:

• chr4-48341768-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020846.2(SLAIN2):​c.29C>T​(p.Ala10Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000479 in 1,378,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: SLAIN2 NM_020846.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.299123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAIN2	NM_020846.2	c.29C>T	p.Ala10Val	missense_variant	1/8	ENST00000264313.11	NP_065897.1
SLAIN2	XM_005248121.4	c.29C>T	p.Ala10Val	missense_variant	1/9		XP_005248178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAIN2	ENST00000264313.11	c.29C>T	p.Ala10Val	missense_variant	1/8	1	NM_020846.2	ENSP00000264313.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000479 AC: 66 AN: 1378168 Hom.: 0 Cov.: 33 AF XY: 0.0000427 AC XY: 29 AN XY: 679492

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000616

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2023

The c.29C>T (p.A10V) alteration is located in exon 1 (coding exon 1) of the SLAIN2 gene. This alteration results from a C to T substitution at nucleotide position 29, causing the alanine (A) at amino acid position 10 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	2.0	M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.017	D
Polyphen		0.90	P
Vest4		0.33
MutPred		0.092		Gain of glycosylation at S6 (P = 0.0615);
MVP		0.15
MPC		0.21
ClinPred		0.92	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1191511299; hg19: chr4-48343785;