rs768841934

Variant names:

• chr1-9730639-C-A
• rs768841934
• NM_001009566.3:c.2815G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-9730639-C-A
• chr1-9730639-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4 BS2

The NM_001009566.3(CLSTN1):​c.2815G>T​(p.Gly939Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G939S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CLSTN1 NM_001009566.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.41
• Publications: 1 publications found

Genes affected

CLSTN1 (HGNC:17447): (calsyntenin 1) This gene is a member of the calsyntenin family, a subset of the cadherin superfamily. The encoded transmembrane protein, also known as alcadein-alpha, is thought to bind to kinesin-1 motors to mediate the axonal anterograde transport of certain types of vesicle. Amyloid precursor protein (APP) is trafficked via these vesicles and so this protein is being investigated to see how it might contribute to the mechanisms underlying Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37700078).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009566.3. 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
	CLSTN1	NM_001009566.3	MANE Select	c.2815G>T	p.Gly939Cys	missense	Exon 19 of 19	NP_001009566.1	O94985-1
	CLSTN1	NM_014944.4		c.2785G>T	p.Gly929Cys	missense	Exon 18 of 18	NP_055759.3	O94985-2
	CLSTN1	NM_001302883.1		c.2758G>T	p.Gly920Cys	missense	Exon 18 of 18	NP_001289812.1	O94985

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLSTN1	ENST00000377298.9	TSL:1 MANE Select	c.2815G>T	p.Gly939Cys	missense	Exon 19 of 19	ENSP00000366513.4	O94985-1
	CLSTN1	ENST00000361311.4	TSL:1	c.2785G>T	p.Gly929Cys	missense	Exon 18 of 18	ENSP00000354997.4	O94985-2
	CLSTN1	ENST00000872287.1		c.2821G>T	p.Gly941Cys	missense	Exon 17 of 17	ENSP00000542346.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458398 Hom.: 0 Cov.: 31 AF XY: 0.00000689 AC XY: 5 AN XY: 725694

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.30
Sift	Benign	0.044	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.16		Gain of helix (P = 0.0496)
MVP		0.40
MPC		0.99
ClinPred		0.94	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.11
Mutation Taster		=55/45	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: rs768841934; hg19: chr1-9790697;